56th-nephrectomy-combination-with-high-salt-diet-nitric-oxide

5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat

Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements ...

University Medical Center Utrecht

The cardiorenal connection.

La connexion cardio-r&eacute;nal.

La connessione cardiorenal.

The incidence of cardiac failure and chronic renal failure is increasing and it has now become clear that the co-existence of the two problems has an extremely bad prognosis. We propose the severe cardiorenal syndrome (SCRS), a pathophysiological condition in which combined cardiac and renal dysfunction amplifies progression of failure of the individual organ, so that cardiovascular morbidity and mortality in this patient group is at least an order of magnitude higher than in the general population. Guyton has provided an excellent framework describing the physiological relationships between cardiac output, extracellular fluid volume control, and blood pressure. While this model is also sufficient to understand systemic haemodynamics in combined cardiac and renal failure, not all aspects of the observed accelerated atherosclerosis, structural myocardial changes, and further decline of renal function can be explained. Since increased activity of the renin-angiotensin system, oxidative stress, inflammation, and increased activity of the sympathetic nervous system seem to be cornerstones of the pathophysiology in combined chronic renal disease and heart failure, we have explored the potential interactions between these cardiorenal connectors. As such, the cardiorenal connection is an interactive network with positive feedback loops, which, in our view, forms the basis for the SCRS.

The severe cardiorenal syndrome: 'Guyton revisited'.

L&#39;incidence de l&#39;insuffisance cardiaque et insuffisance r&eacute;nale chronique augmente et il est d&eacute;sormais clair que la coexistence des deux probl&egrave;mes a un tr&egrave;s mauvais pronostic. Nous vous proposons le syndrome cardio-r&eacute;nal s&eacute;v&egrave;re (SCRS), un &Eacute;tat physiopathologique dans lequel combin&eacute; dysfonction cardiaque et r&eacute;nale amplifie la progression de l&#39;insuffisance de l&#39;organe individuel, afin que la morbidit&eacute; cardiovasculaire et la mortalit&eacute; dans ce groupe de patients est au moins un ordre de grandeur plus &eacute;lev&eacute; que dans la population g&eacute;n&eacute;rale. Guyton a fourni un excellent cadre d&eacute;crivant les relations physiologiques entre le d&eacute;bit cardiaque, contr&ocirc;le du volume du liquide extracellulaire et la pression art&eacute;rielle. Si ce mod&egrave;le est &eacute;galement suffisant pour comprendre l&#39;h&eacute;modynamique syst&eacute;mique en combin&eacute; cardiaque et insuffisance r&eacute;nale, pas tous les aspects de l&#39;ath&eacute;roscl&eacute;rose acc&eacute;l&eacute;r&eacute;e observ&eacute;e, des changements structurels myocardiques et encore le d&eacute;clin de la fonction r&eacute;nale peuvent &ecirc;tre expliqu&eacute;es. Depuis l&#39;augmentation de l&#39;activit&eacute; du syst&egrave;me r&eacute;nine-angiotensine, stress oxydatif, l&#39;inflammation et augmentation de l&#39;activit&eacute; du syst&egrave;me nerveux sympathique semblent &ecirc;tre les pierres angulaires de la physiopathologie en combin&eacute; de maladie r&eacute;nale chronique et l&#39;insuffisance cardiaque, nous avons explor&eacute; les interactions potentielles entre ces connecteurs cardio-r&eacute;nal. Par cons&eacute;quent, la connexion cardio-r&eacute;nal est un r&eacute;seau interactif avec des boucles de r&eacute;troaction positive, qui, &agrave; notre avis, constitue la base pour le SCRS.

Le syndrome cardio-r&eacute;nal s&eacute;v&egrave;re: &laquo; Guyton revisit&eacute; &raquo;.

L&#39;incidenza di insufficienza cardiaca e insufficienza renale cronica &egrave; in aumento ed ora &egrave; diventato chiaro che la coesistenza dei due problemi ha una pessima prognosi. Vi proponiamo la sindrome grave cardiorenal (SCR), una condizione fisiopatologica in cui combinato disfunzione cardiaca e renale amplifica la progressione della insufficienza dell&#39;organo individuale, cos&igrave; che la morbilit&agrave; cardiovascolare e la mortalit&agrave; in questo gruppo di pazienti &egrave; almeno un ordine di grandezza superiore rispetto alla popolazione generale. Guyton ha fornito un quadro eccellente che descrive i rapporti fisiologici tra gittata cardiaca, controllo di volume del liquido extracellulare e pressione sanguigna. Mentre questo modello &egrave; inoltre sufficiente per capire l&#39;emodinamica sistemica in combinato cardiaco e insufficienza renale, non tutti gli aspetti del osservati accelerata aterosclerosi, cambiamenti strutturali del miocardio e ulteriore declino della funzione renale possono essere spiegati. Dall&#39;aumento dell&#39;attivit&agrave; del sistema renina-angiotensina, stress ossidativo, infiammazione e aumento dell&#39;attivit&agrave; del sistema nervoso simpatico sembrano essere pietre miliari della fisiopatologia in combinata della malattia renale cronica e insufficienza cardiaca, abbiamo esplorato le potenziali interazioni tra questi connettori cardiorenal. Come tale, la connessione cardiorenal &egrave; una rete interattiva con anelli di retroazione positiva, che, a nostro avviso, costituisce la base per il SCR.

La sindrome grave cardiorenal: &#39;Guyton rivisitato&#39;.

The cardiorenal syndrome a classification into 4 groups?

Le syndrome cardio-r&eacute;nal une classification en 4 groupes ?

La sindrome cardiorenal una classificazione in 4 gruppi?

Renal venous congestion and renal function in congestive heart failure.

Congestion veineuse r&eacute;nale et la fonction r&eacute;nale dans l&#39;insuffisance cardiaque congestive.

Congestione venosa renale e la funzione renale in insufficienza cardiaca congestizia.

We recently developed a rat model of cardiorenal failure that is characterized by severe left ventricular systolic dysfunction (LVSD) and low nitric oxide (NO) production that persisted after temporary low-dose NO synthase inhibition. We hypothesized that LVSD was due to continued low NO availability and might be reversed by supplementing NO. Rats underwent a subtotal nephrectomy and were treated with low-dose NO synthase inhibition with N(Ï‰)-nitro-l-arginine up to week 8. After 3 wk of washout, rats were treated orally with either the long-acting, tolerance-free NO donor molsidomine (Mols) or vehicle (Veh). Cardiac and renal function were measured on weeks 11, 13, and 15. On week 16, LV hemodynamics and pressure-volume relationships were measured invasively, and rats were killed to quantify histological damage. On week 15, blood pressure was mildly reduced and creatinine clearance was increased by Mols (both P < 0.05). Mols treatment improved ejection fraction (53 Â± 3% vs. 37 Â± 2% in Veh-treated rats, P < 0.001) and stroke volume (324 Â± 33 vs. 255 Â± 15 Î¼l in Veh-treated rats, P < 0.05). Rats with Mols treatment had lower end-diastolic pressures (8.5 Â± 1.1 mmHg) than Veh-treated rats (16.3 Â± 3.5 mmHg, P < 0.05) and reduced time constants of relaxation (21.9 Â± 1.8 vs. 30.9 Â± 3.3 ms, respectively, P < 0.05). The LV end-systolic pressure-volume relationship was shifted to the left in Mols compared with Veh treatment. In summary, in a model of cardiorenal failure with low NO availability, supplementing NO significantly improves cardiac systolic and diastolic function without a major effect on afterload.

The nitric oxide donor molsidomine rescues cardiac function in rats with chronic kidney disease and cardiac dysfunction.

Nous avons r&eacute;cemment mis au point un mod&egrave;le de rat de d&eacute;faillance cardio-r&eacute;nal qui se caract&eacute;rise par une dysfonction systolique ventriculaire gauche (LVSD) et de faible production d&#39;oxyde nitrique (non) qui ne persistaient apr&egrave;s minidos&eacute;s temporaire aucune inhibition synthase. Nous avons &eacute;mis l&#39;hypoth&egrave;se que LVSD &eacute;tait d&ucirc; &agrave; faible aucune disponibilit&eacute; et peut &ecirc;tre invers&eacute; en compl&eacute;tant no Rat a subi une n&eacute;phrectomie sous-total et ont &eacute;t&eacute; ne trait&eacute;s avec faibles doses aucune inhibition synthase avec N (&omega;) - nitro - l-arginine jusqu&#39;&agrave; la semaine 8. Apr&egrave;s 3 semaines de sevrage, rats ont &eacute;t&eacute; trait&eacute;s par voie orale avec soit la long-action, exempt de tol&eacute;rance aucun donneur molsidomine (Mols) ou un v&eacute;hicule (Veh). La fonction r&eacute;nale et cardiaque ont &eacute;t&eacute; mesur&eacute;s sur les semaines 11, 13 et 15. Semaine 16, les relations h&eacute;modynamique et pression-volume de LV ont &eacute;t&eacute; mesur&eacute;es invasive des rats ont &eacute;t&eacute; tu&eacute;s afin de quantifier les dommages histologiques. Semaine 15, pression art&eacute;rielle a &eacute;t&eacute; l&eacute;g&egrave;rement r&eacute;duite et la clairance de la cr&eacute;atinine a &eacute;t&eacute; augment&eacute; de Mols (les deux P &lt; 0,05). Fraction d&#39;&eacute;jection am&eacute;lior&eacute;e de traitement Mols (53 &plusmn; 3 % vs 37 &plusmn; 2 % chez les rats trait&eacute;s Veh, P &lt; 0,001) et volume de la course (324 &plusmn; 33 contre 255 &plusmn; 15 &mu;l chez les rats trait&eacute;s Veh, P 0,05 &lt;). Rats avec traitement Mols ont eu de plus basse pression t&eacute;l&eacute;diastolique (8,5 &plusmn; 1,1 mmHg) que chez les rats trait&eacute;s Veh (16,3 &plusmn; 3,5 mmHg, P 0,05 &lt;) et r&eacute;duit les constantes de temps de relaxation (21,9 &plusmn; 1,8 contre 30,9 &plusmn; 3,3 ms, respectivement, P &lt; 0,05). La relation pression-volume t&eacute;l&eacute;systolique de LV a &eacute;t&eacute; d&eacute;cal&eacute;e vers la gauche en Mols compar&eacute;e traitement v&eacute;h. En r&eacute;sum&eacute;, dans un mod&egrave;le d&#39;&eacute;chec cardio-r&eacute;nal non faible disponibilit&eacute;, compl&eacute;tant non significativement am&eacute;liore la fonction cardiaque systolique et diastolique sans effet majeur sur la postcharge.

La molsidomine donneur de monoxyde d&#39;azote sauve la fonction cardiaque chez les rats atteints d&#39;une dysfonction cardiaque et de maladie r&eacute;nale chronique.

Abbiamo recentemente sviluppato un modello di ratto cardiorenal fallimento che &egrave; caratterizzata da grave disfunzione sistolica ventricolare sinistra (LVSD) e bassa l&#39;ossido nitrico (NO) produzione che non persisteva dopo la basso-dose temporanea inibizione sintasi. Abbiamo ipotizzato che LVSD non era dovuto continuato basso nessuna disponibilit&agrave; e potrebbe essere invertito completandola n. Ratti sono stati sottoposti a nefrectomia parziale e sono stati non trattati con basse dosi sintasi inibizione con N (&omega;) - nitro - l-arginina fino a 8 settimane. Dopo 3 sett di washout, ratti sono stati trattati per via orale con entrambi il long-acting, tolleranza senza nessun donatore molsidomine (Mols) o veicolo (Veh). Funzione cardiaca e renale sono stati misurati su settimane 11, 13 e 15. Settimana 16, relazioni di emodinamica e pressione-volume LV sono state misurate in modo invasivo e ratti sono stati uccisi per quantificare il danno istologico. Settimana 15, pressione sanguigna &egrave; stato leggermente ridotto e clearance della creatinina &egrave; stata aumentata da Mols (entrambi P &lt; 0,05). Frazione di eiezione maggiore del trattamento Mols (53 &plusmn; 3% vs 37 &plusmn; 2% nei ratti trattati con Veh, P &lt; 0,001) e stroke volume (324 &plusmn; 33 vs 255 &plusmn; 15 &mu;l nei ratti trattati con Veh, P &lt; 0,05). Ratti con trattamento Mols avevano basse pressioni di fine diastole (8,5 &plusmn; 1,1 mmHg) di ratti trattati con Veh (16,3 &plusmn; 3,5 mmHg, P &lt; 0,05) e ridotto costanti in fase di rilassamento (21,9 &plusmn; 1,8 vs 30,9 &plusmn; 3,3 ms, rispettivamente, P &lt; 0,05). La relazione di fine-sistolico pressione-volume LV &egrave; stata spostata a sinistra in Mols confrontato con trattamento Veh. In sintesi, in un modello di guasto cardiorenal con bassa NO disponibilit&agrave;, integrando significativamente NO migliora la funzione sistolica e diastolica cardiaca senza un effetto importante su afterload.

L&#39;ossido nitrico donatori molsidomine Salva funzione cardiaca nei topi con renale cronica malattia e cardiaci disfunzione.

La matrice extracellulaire peut-&ecirc;tre induire des r&eacute;ponses inflammatoires pr&eacute;judiciables sur la d&eacute;gradation, causant des ind&eacute;sirables de remodelage cardiaque et insuffisance cardiaque. La matrice extracellulaire prot&eacute;ines fibronectine-EDA (EIIIA ; EDA) est augment&eacute;e apr&egrave;s l&eacute;sion tissulaire et peut servir d&#39;un &quot;signal de danger&quot; pour les leucocytes de causer des effets ind&eacute;sirables cardiaques remodelage apr&egrave;s infarctus du myocarde.

Manque de fibronectine-EDA favorise la survie et emp&ecirc;che les ind&eacute;sirable d&eacute;t&eacute;rioration de fonction remodelage et cardiaque apr&egrave;s infarctus du myocarde.

La matrice extracellulare pu&ograve; indurre risposte infiammatorie dannose sulla degradazione, causando avverso rimodellamento cardiaco e insufficienza cardiaca. La matrice extracellulare della proteina fibronectina-EDA (EIIIA; EDA) &egrave; sovraregolati dopo lesioni tessutali e pu&ograve; agire come un &quot;segnale di pericolo&quot; per leucociti a causare cardiaci avversi rimodellamento dopo infarto.

Mancanza di fibronectina-EDA promuove la sopravvivenza e previene il deterioramento funzione avverso rimodellamento e cuore dopo infarto miocardico.

The extracellular matrix may induce detrimental inflammatory responses on degradation, causing adverse cardiac remodeling and heart failure. The extracellular matrix protein fibronectin-EDA (EIIIA; EDA) is upregulated after tissue injury and may act as a "danger signal" for leukocytes to cause adverse cardiac remodeling after infarction.

Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction.

Coexistence of chronic kidney disease (CKD) and heart failure (HF) in humans is associated with poor outcome. We hypothesized that preexistent CKD worsens cardiac outcome after myocardial infarction, and conversely that ensuing HF worsens progression of CKD. Subtotally nephrectomized (SNX) or sham-operated (CON) rats were subjected to coronary ligation (CL) or sham surgery in week 9 to realize four groups: CON, SNX, CON + CL, and SNX + CL. Blood pressure and renal function were measured in weeks 8, 11, 13, and 15. In week 16, cardiac hemodynamics and end-organ damage were assessed. Blood pressure was significantly lower in SNX + CL vs. SNX. Despite this, glomerulosclerosis was more severe in SNX + CL vs. SNX. Two weeks after CL, SNX + CL had more cardiac dilatation compared with CON + CL (end-diastolic volume index: 0.28 Â± 0.04 vs. 0.19 Â± 0.03 ml/100 g body wt; mean Â± SD, P < 0.001), although infarct size was similar. During follow-up in SNX + CL, ejection fraction declined. Mortality was only observed in SNX + CL (2 out of 9). In SNX + CL, end-diastolic pressure (18 Â± 4 mmHg) and tau (29 Â± 9 ms), the time constant of active relaxation, were significantly higher compared with SNX (13 Â± 3 mmHg, 20 Â± 4 ms; P < 0.01) and CON + CL (11 Â± 5 mmHg, 17 Â± 2 ms; P < 0.01). The diameter of small arterioles in the myocardium was significantly decreased in SNX + CL vs. CON + CL (P < 0.01). Urinary excretion of NO metabolites was significantly lower in SNX + CL compared with both CL and SNX. This study demonstrates the existence of more heart and more kidney damage in a new model of combined CKD and HF than in the individual models. Such enhanced damage appears to be separate from systemic hemodynamic changes. Reduced nitric oxide availability may have played a role in both worsened glomerulosclerosis and cardiac diastolic function and appears to be a connector in the cardiorenal syndrome.

Subtotal nephrectomy plus coronary ligation leads to more pronounced damage in both organs than either nephrectomy or coronary ligation.

Coexistence de l&#39;insuffisance r&eacute;nale chronique (IRC) et insuffisance cardiaque (IC) chez l&#39;homme est associ&eacute; de mauvais pronostic. Nous avons &eacute;mis l&#39;hypoth&egrave;se que CKD pr&eacute;existants s&#39;aggrave r&eacute;sultat cardiaque apr&egrave;s infarctus du myocarde, et inversement que HF qui s&#39;ensuit s&#39;aggrave la progression de l&#39;IRC. Subtotally n&eacute;phrectomis&eacute; (SNX) ou rats (CON) op&eacute;r&eacute;s ont &eacute;t&eacute; soumis &agrave; la ligature coronaire (CL) ou de la chirurgie de l&#39;imposture en semaine 9 de r&eacute;aliser quatre groupes : CON, SNX, CON + CL et SNX + CL. tension art&eacute;rielle et la fonction r&eacute;nale ont &eacute;t&eacute; mesur&eacute;s en semaines, 8, 11, 13 et 15. Semaine 16, h&eacute;modynamique cardiaque et dommages d&#39;extr&eacute;mit&eacute;-organe ont &eacute;t&eacute; &eacute;valu&eacute;es. La pression art&eacute;rielle a &eacute;t&eacute; significativement plus faible chez SNX + CL vs SNX. Malgr&eacute; cela, glom&eacute;ruloscl&eacute;rose a &eacute;t&eacute; plus s&eacute;v&egrave;re dans SNX + CL vs SNX. Deux semaines apr&egrave;s CL, SNX + CL eu plus de dilatation cardiaque par rapport &agrave; CON + CL (index de volume t&eacute;l&eacute;diastolique : 0,28 &plusmn; 0,04 contre 0,19 &plusmn; 0,03 ml/100 g de poids corporel ; moyenne &plusmn; &eacute;cart-type, P &lt; 0,001), bien que la taille de l&#39;infarctus a &eacute;t&eacute; similaire. Au cours du suivi en SNX + CL, la fraction d&#39;&eacute;jection a diminu&eacute;. La mortalit&eacute; a &eacute;t&eacute; observ&eacute;e seulement SNX + CL (2 sur 9). SNX + CL, pression t&eacute;l&eacute;diastolique (18 &plusmn; 4 mmHg) et tau (29 &plusmn; 9 ms), la constante de temps de d&eacute;tente active, &eacute;taient significativement plus &eacute;lev&eacute;s comparativement &agrave; SNX (13 &plusmn; 3 mmHg, 20 &plusmn; 4 ms ; P &lt; 0,01) et CON + CL (11 &plusmn; 5 mmHg, 17 &plusmn; 2 ms ; P &lt; 0,01). Le diam&egrave;tre des petites art&eacute;rioles dans le myocarde a diminu&eacute; significativement en SNX + CL vs CON + CL (P &lt; 0,01). L&#39;excr&eacute;tion urinaire d&#39;aucun m&eacute;tabolite &eacute;tait significativement plus faible chez SNX + CL compar&eacute;e aux CL et SNX. Cette &eacute;tude d&eacute;montre l&#39;existence de plus de coeur et plus de dommages aux reins dans un nouveau mod&egrave;le de combin&eacute; CKD et HF que dans les mod&egrave;les individuels. Ces dommages am&eacute;lior&eacute;s semblent &ecirc;tre distinct de changements h&eacute;modynamiques syst&eacute;miques. Disponibilit&eacute; r&eacute;duite l&#39;oxyde nitrique peut ont jou&eacute; un r&ocirc;le en glom&eacute;ruloscl&eacute;rose aggrav&eacute;e et la fonction cardiaque diastolique et semble &ecirc;tre un connecteur dans le syndrome cardio-r&eacute;nal.

Sous-total n&eacute;phrectomie et ligature coronaire entra&icirc;ne plus prononc&eacute;e des dommages dans les deux organes que n&eacute;phrectomie ou ligature coronaire.

Coesistenza di malattia renale cronica (CKD) e insufficienza cardiaca (HF) negli esseri umani &egrave; associata a prognosi sfavorevole. Abbiamo ipotizzato che CKD preesistenti peggiora outcome cardiaco dopo infarto miocardico, e al contrario quello conseguente HF peggiora la progressione dell&#39;insufficienza renale cronica. Subtotally nephrectomized (SNX) o sham-operated (CON) ratti sono stati sottoposti a legatura coronarica (CL) o chirurgia sham nella settimana 9 di realizzare quattro gruppi: CON, SNX, CON + CL e SNX + CL. pressione arteriosa e la funzione renale sono stati misurati in settimane, 8, 11, 13 e 15. Settimana 16, emodinamica cardiaca e danno d&#39;organo fine sono stati valutati. Pressione sanguigna era significativamente pi&ugrave; bassa nel SNX + CL vs SNX. Nonostante questo, era pi&ugrave; severa in SNX + CL vs SNX glomerulosclerosi. Due settimane dopo la CL, SNX + CL aveva pi&ugrave; dilatazione cardiaca rispetto CON + CL (indice di volume di fine diastole: 0,28 &plusmn; 0.04 vs 0,19 &plusmn; 0,03 ml/100 g corpo wt; media &plusmn; SD, P &lt; 0.001), anche se il formato di infarto era simile. Durante il follow-up a SNX + CL, frazione di eiezione &egrave; diminuita. Mortalit&agrave; &egrave; stata osservata solo in SNX + CL (2 su 9). Nella SNX + CL, fine-diastole (18 &plusmn; 4 mmHg) e tau (29 &plusmn; 9 ms), la costante di tempo di rilassamento attivo, erano significativamente pi&ugrave; elevati rispetto alla SNX (13 &plusmn; 3 mmHg, 20 &plusmn; 4 ms; P &lt; 0,01) e CON + CL (11 &plusmn; 5 mmHg, 17 &plusmn; 2 ms; P &lt; 0,01). Il diametro delle arteriole piccole nel miocardio era notevolmente diminuito in SNX + CL vs CON + CL (P &lt; 0,01). Escrezione urinaria di metaboliti non era significativamente pi&ugrave; basso nel SNX + CL rispetto sia con CL e SNX. Questo studio dimostra l&#39;esistenza di pi&ugrave; cuore e pi&ugrave; danni renali in un nuovo modello di combinato CKD e HF rispetto a singoli modelli. Tale danno maggiore sembra essere separato da cambiamenti emodinamici sistemici. L&#39;ossido nitrico ridotta disponibilit&agrave; possa aver giocato un ruolo sia peggiorata glomerulosclerosi e funzione diastolica cardiaca e sembra essere un connettore nella sindrome cardiorenal.

Subtotale nefrectomia plus coronarica legatura conduce a pi&ugrave; pronunciato danni in entrambi gli organi rispetto a nefrectomia o legatura coronarica.

Chronic kidney disease (CKD) is a major health care problem. New interventions to slow or prevent disease progression are urgently needed. We studied functional and structural effects of infusion of healthy and CKD bone marrow cells (BMCs) in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX) in Lewis rats, and disease progression was accelerated with L-NNA and 6% NaCl diet. Six weeks after SNX, CKD rats received healthy eGFPâºBMCs, CKD eGFPâºBMCs, or vehicle by single renal artery injection. Healthy BMCs were functionally effective six weeks after administration: glomerular filtration rate (GFR; inulin clearance) (0.48Â±0.16 vs. 0.26Â±0.14 ml/min/100gr) and effective renal plasma flow (RPF; PAH clearance) (1.6Â±0.40 vs. 1.0Â±0.62 ml/min/100gr) were higher in healthy BMC- vs. vehicle-treated rats (both p<0.05). Systolic blood pressure and proteinuria were lower five weeks after treatment with healthy BMCs vs. vehicle (SBP; 151Â±13 vs.186Â±25 mm Hg, proteinuria; 33Â±20 vs. 59Â±39 mg/d, both p<0.05). Glomerular capillary density was increased and less sclerosis was detected after healthy BMC (both p<0.05). Tubulo-interstitial inflammation was also decreased after healthy BMC. eGFPâº cells were present in the glomeruli and peritubular capillaries of the remnant kidney in all BMC-treated rats. CKD BMCs also reduced SBP, proteinuria, glomerulosclerosis and tubular atrophy vs. vehicle in CKD rats. However, CKD BMC therapy was not functionally effective vs. vehicle: GFR: 0.28Â±0.09 vs.0.26Â±0.16 ml/min/100gr (NS), RPF: 1.15Â±0.36 vs. 0.78Â±0.44 vs. ml/min/100gr (NS), and failed to decrease tubulo-interstitial inflammation and fibrosis.Single intrarenal injection of healthy BMCs in rats with established CKD slowed progression of the disease, associated with increased glomerular capillary density and less sclerosis, whereas injection of CKD BMCs was less effective.

HEALTHY BONE MARROW CELLS REDUCE PROGRESSION OF KIDNEY FAILURE BETTER THAN CKD BONE MARROW CELLS IN RATS WITH ESTABLISHED CHRONIC KIDNEY DISEASE.

Insuffisance r&eacute;nale chronique (IRC) est un probl&egrave;me de sant&eacute; majeur. Nouvelles interventions &agrave; ralentir ou emp&ecirc;cher la progression de la maladie sont n&eacute;cessaires d&#39;urgence. Nous avons &eacute;tudi&eacute; les effets fonctionnels et structurels d&#39;une perfusion de sain et de cellules de moelle osseuse CKD (CR) dans un mod&egrave;le de rat de CKD &eacute;tabli. CKD a &eacute;t&eacute; induite par n&eacute;phrectomie 5/6 (SNX) chez les rats Lewis et progression de la maladie s&#39;est acc&eacute;l&eacute;r&eacute;e avec la L-NNA et r&eacute;gime contenant 6 % de NaCl. Six semaines apr&egrave;s SNX, CKD rats ont re&ccedil;u eGFP&#x207A;BMCs sain, CKD eGFP&#x207A;BMCs ou v&eacute;hicule par injection unique de l&#39;art&egrave;re r&eacute;nale. Des concentrations de r&eacute;f&eacute;rence en sant&eacute; &eacute;taient fonctionnellement efficaces six semaines apr&egrave;s l&#39;administration : le taux de filtration glom&eacute;rulaire (GFR, clairance de l&#39;inuline) (0.48&plusmn;0.16 vs 0.26&plusmn;0.14 ml/min/100 gr) et d&eacute;bit plasmatique r&eacute;nal efficace (FPR ; D&eacute;gagement de PAH) (1.6&plusmn;0.40 vs 1.0&plusmn;0.62 ml/min/100 gr) &eacute;taient plus &eacute;lev&eacute;es en BMC sain-vs rats trait&eacute;s au v&eacute;hicule (les deux p &lt; 0,05). La pression art&eacute;rielle systolique et la prot&eacute;inurie &eacute;taient inf&eacute;rieurs cinq semaines apr&egrave;s le traitement avec BMC sain vs v&eacute;hicule (SBP ; 151&plusmn;13 vs.186&plusmn;25 mm Hg, prot&eacute;inurie ; 33&plusmn;20 vs 59&plusmn;39 mg/j, les deux p &lt; 0,05). Densit&eacute; capillaire glom&eacute;rulaire augmente et moins la scl&eacute;rose en plaques a &eacute;t&eacute; d&eacute;tect&eacute;e apr&egrave;s BMC sain (les deux p &lt; 0,05). Inflammation tubulo-interstitielle a &eacute;t&eacute; &eacute;galement diminu&eacute;e apr&egrave;s BMC sain. les cellules eGFP&#x207A; sont pr&eacute;sents dans les glom&eacute;rules et p&eacute;ritubulaire capillaires du rein reste dans tous les rats trait&eacute;s au BMC. CKD ca r&eacute;duit aussi SBP, prot&eacute;inurie, glom&eacute;ruloscl&eacute;rose et atrophie des tubes vs v&eacute;hicule chez les rats CKD. Th&eacute;rapie de CKD BMC n&#39;&eacute;tait cependant pas fonctionnellement efficace contre v&eacute;hicule : GFR : 0.28&plusmn;0.09 vs.0.26&plusmn;0.16 ml/min/100 gr (NS), RPF : 1.15&plusmn;0.36 vs 0.78&plusmn;0.44 vs ml/min/100 gr (NS) et n&#39;a pas pu diminuer inflammation tubulo-interstitielle et fibrose.Une seule injection intrar&eacute;nale de BMC saine chez les rats d&#39;IRC &eacute;tabli a ralenti la progression de la maladie, associ&eacute;e li&eacute;e la densit&eacute; capillaire glom&eacute;rulaire accrue et moins de scl&eacute;rose en plaques, alors que l&#39;injection de CKD CR &eacute;tait moins efficace.

LES CELLULES SAINES DE LA MOELLE OSSEUSE R&Eacute;DUISENT LA PROGRESSION DE L&#39;INSUFFISANCE R&Eacute;NALE MIEUX QUE CKD CELLULES DE LA MOELLE OSSEUSE CHEZ DES RATS ATTEINTS D&#39;INSUFFISANCE R&Eacute;NALE CHRONIQUE &Eacute;TABLIS.

Malattia renale cronica (CKD) &egrave; un grave problema sanitario. Sono urgentemente necessari nuovi interventi per rallentare o prevenire la progressione della malattia. Abbiamo studiato gli effetti funzionali e strutturali dell&#39;infusione di sano e cellule di midollo osseo CKD (BMC) in un modello del ratto di CKD stabilito. CKD &egrave; stata indotta da 5/6 nefrectomia (SNX) nei ratti Lewis, e la progressione della malattia &egrave; stata accelerata con L-NNA e 6% NaCl dieta. Sei settimane dopo SNX, ratti CKD ricevuto eGFP&#x207A;BMCs sano, eGFP&#x207A;BMCs CKD o veicolo da iniezione singola arteria renale. BMC sani erano funzionalmente efficace sei settimane dopo la somministrazione: tasso di filtrazione glomerulare (GFR; clearance inulina) (0.48&plusmn;0.16 vs 0.26&plusmn;0.14 ml/min/100gr) e flusso di plasma efficace renale (RPF; PAH clearance) (1.6&plusmn;0.40 vs 1.0&plusmn;0.62 ml/min/100gr) erano pi&ugrave; elevati nel sano BMC-vs ratti trattati con veicolo (entrambi p &lt; 0,05). Pressione arteriosa sistolica e proteinuria erano inferiori cinque settimane dopo il trattamento con BMC sani vs. veicolo (SBP; 151&plusmn;13 vs.186&plusmn;25 mm Hg, proteinuria; 33&plusmn;20 vs 59&plusmn;39 mg/d, entrambi p &lt; 0,05). Densit&agrave; capillare glomerulare &egrave; stato aumentato e meno sclerosi &egrave; stata rilevata dopo sano BMC (entrambi p &lt; 0,05). Infiammazione tubulo-interstiziale &egrave; stato anche diminuito dopo BMC sano. eGFP&#x207A; cellule erano presenti nei glomeruli e peritubulare capillari del rene residuo in tutti i ratti trattati con BMC. CKD BMC ridotto anche SBP, proteinuria, glomerulosclerosi e atrofia tubulare vs veicolo in ratti CKD. Tuttavia, non era funzionalmente efficacia vs veicolo terapia CKD BMC: GFR: 0.28&plusmn;0.09 vs.0.26&plusmn;0.16 ml/min/100gr (NS), RPF: 1.15&plusmn;0.36 vs. 0.78&plusmn;0.44 vs ml/min/100gr (NS) e non &egrave; riuscito a diminuire l&#39;infiammazione tubulo-interstiziale e fibrosi.Singola iniezione intrarenale del BMC sano nei ratti con CKD stabilito ha rallentato la progressione della malattia, associata con maggiore densit&agrave; di capillari glomerulari e meno sclerosi, considerando che l&#39;iniezione di CKD BMC era meno efficace.

LE CELLULE DEL MIDOLLO OSSEO SANO RIDUCONO LA PROGRESSIONE DELLA INSUFFICIENZA RENALE MEGLIO DI CKD CELLULE DEL MIDOLLO OSSEO NEI RATTI CON MALATTIA RENALE CRONICA STABILITI.

La combinazione della malattia renale cronica (CKD) e insufficienza cardiaca (HF) &egrave; associata con una prognosi infausta. Sebbene gli studi clinici suggeriscono un&#39;interazione bidirezionale specifico tra HF e CKD, comprensione della patogenesi della sindrome cardiorenal (CRS) rimane limitata. Noi esaminare prove disponibili su interazioni cardiorenal da modelli animali di insufficienza renale cronica e HF e discutere diversi studi che utilizzava un modello &quot;double-hit&quot; all&#39;organo di ricerca cross talk tra il cuore e i reni. Per quanto riguarda cardiaci cambiamenti nei modelli CKD, parametri di rimodellamento cardiaco sono equivoci e funzione sistolica cardiaca rimane generalmente conservata. Cambiamenti strutturali comprendono ipertrofia, fibrosi e microvasculopathy. Nei modelli di HF, dati sulla patologia renale sono per lo pi&ugrave; limitati ai cambiamenti emodinamici funzionale. La maggior parte dei modelli di doppio-colpo erano in grado di mostrare che combinato danno cardiaco e renale induce additivo danni ad entrambi gli organi, forse a causa del studio di breve durata o assenza di insufficienza di organo. A causa di questa mancanza di modelli &quot;dual-fallimento&quot;, abbiamo sviluppato due modelli di ratto di combinato CKD e HF in cui disfunzione renale indotta da una disfunzione cardiaca subtotale nefrectomia preceduto. Disfunzione cardiaca &egrave; stata indotta o funzionalmente dalla deplezione di ossido nitrico o strutturalmente da infarto del miocardio. In entrambi i modelli, abbiamo scoperto che il rimodellamento cardiaco e fallimento erano peggiori in CKD ratti rispetto ai controlli, subendo l&#39;insulto cardiaco stesso. Variabili di danno renale, come glomerulosclerosi e della proteinuria, erano anche ulteriormente aggravate da lesioni cardiorenal combinato. Questi studi talk show target organo trasversale che si verificano nel CRS. Questi modelli possono essere utili per gli studi interventistici nei ratti.

Organo bersaglio cross talk cardiorenal syndrome: modelli animali.

The combination of chronic kidney disease (CKD) and heart failure (HF) is associated with an adverse prognosis. Although clinical studies hint at a specific bidirectional interaction between HF and CKD, insight into the pathogenesis of cardiorenal syndrome (CRS) remains limited. We review available evidence on cardiorenal interactions from animal models of CKD and HF and discuss several studies that employed a "double-hit" model to research organ cross talk between the heart and kidneys. Regarding cardiac changes in CKD models, parameters of cardiac remodeling are equivocal and cardiac systolic function generally remains preserved. Structural changes include hypertrophy, fibrosis, and microvasculopathy. In models of HF, data on renal pathology are mostly limited to functional hemodynamic changes. Most double-hit models were unable to show that combined renal and cardiac injury induces additive damage to both organs, perhaps because of the short study duration or absence of organ failure. Because of this lack of "dual-failure" models, we have developed two rat models of combined CKD and HF in which renal dysfunction induced by a subtotal nephrectomy preceded cardiac dysfunction. Cardiac dysfunction was induced either functionally by nitric oxide depletion or structurally by myocardial infarction. In both models, we found that cardiac remodeling and failure were worse in CKD rats compared with controls undergoing the same cardiac insult. Variables of renal damage, like glomerulosclerosis and proteinuria, were also further worsened by combined cardiorenal injury. These studies show that target organ cross talk does occur in CRS. These models may be useful for interventional studies in rats.

Target organ cross talk in cardiorenal syndrome: animal models.

La combinaison de l&#39;insuffisance r&eacute;nale chronique (IRC) et insuffisance cardiaque (IC) est associ&eacute;e &agrave; un pronostic d&eacute;favorable. Bien que des &eacute;tudes cliniques laissent entrevoir une interaction sp&eacute;cifique bidirectionnelle entre HF et CKD, aper&ccedil;u de la pathog&eacute;nie du syndrome cardio-r&eacute;nal (CRS) reste limit&eacute;. Nous allons examiner les preuves disponibles sur les interactions cardior&eacute;nale de mod&egrave;les animaux de CKD et HF et discuter de plusieurs &eacute;tudes qui ont utilis&eacute; un mod&egrave;le &laquo; double-coup &raquo; &agrave; l&#39;organe de recherche la diaphonie entre le c&oelig;ur et les reins. Concernant les modifications cardiaques dans les mod&egrave;les CKD, param&egrave;tres de remodelage cardiaque sont &eacute;quivoques et fonction systolique cardiaque reste g&eacute;n&eacute;ralement pr&eacute;serv&eacute;e. Changements structurels comprennent l&#39;hypertrophie, fibrose et microvasculopathie. Dans les mod&egrave;les de HF, donn&eacute;es sur la pathologie r&eacute;nale sont principalement limit&eacute;es &agrave; des modifications h&eacute;modynamiques fonctionnelles. La plupart des mod&egrave;les double-hit n&#39;ont pas montrer que combin&eacute;e de l&eacute;sion r&eacute;nale et cardiaque induit additif endommager les deux organes, peut-&ecirc;tre &agrave; cause de l&#39;&eacute;tude de courte dur&eacute;e ou l&#39;absence de d&eacute;faillance polyvisc&eacute;rale. En raison de cette absence de mod&egrave;les de &quot;double-&eacute;chec&quot;, nous avons d&eacute;velopp&eacute; deux mod&egrave;les de rat de CKD et HF combin&eacute;s dans laquelle dysfonction r&eacute;nale induite par un dysfonctionnement cardiaque sous-total n&eacute;phrectomie pr&eacute;c&eacute;d&eacute;. Dysfonctionnement cardiaque a &eacute;t&eacute; induit soit fonctionnellement par l&#39;appauvrissement de l&#39;oxyde nitrique ou structurellement par infarctus du myocarde. Dans les deux mod&egrave;les, nous avons constat&eacute; que remodelage cardiaque et l&#39;&eacute;chec &eacute;taient pires chez les rats CKD compar&eacute;es aux t&eacute;moins subissant la m&ecirc;me insulte cardiaque. Variables de dommages aux reins, comme l&#39;industrie de la construction et de la prot&eacute;inurie, glom&eacute;ruloscl&eacute;rose &eacute;taient aussi encore aggrav&eacute;es par blessure combin&eacute;e cardio-r&eacute;nal. Ces &eacute;tudes montrent que cibler l&#39;organe cross talk se produit-elle &agrave; Sir. Ces mod&egrave;les peuvent &ecirc;tre utiles pour les &eacute;tudes interventionnelles chez les rats.

Organe cible la diaphonie dans le syndrome cardio-r&eacute;nal : mod&egrave;les animaux.

Chronic kidney disease (CKD) is a major health care problem. New interventions to slow or prevent disease progression are urgently needed. We studied functional and structural effects of infusion of healthy and CKD bone marrow cells (BMCs) in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX) in Lewis rats, and disease progression was accelerated with L-NNA and 6% NaCl diet. Six weeks after SNX, CKD rats received healthy eGFP(+) BMCs, CKD eGFP(+) BMCs, or vehicle by single renal artery injection. Healthy BMCs were functionally effective 6 weeks after administration: glomerular filtration rate (GFR; inulin clearance) (0.48Â±0.16 vs. 0.26Â±0.14 ml/min/100 g) and effective renal plasma flow (RPF; PAH clearance) (1.6Â±0.40 vs. 1.0Â±0.62 ml/min/100 g) were higher in healthy BMC- versus vehicle-treated rats (both p < 0.05). Systolic blood pressure (SBP) and proteinuria were lower 5 weeks after treatment with healthy BMCs versus vehicle (SBP, 151Â±13 vs. 186Â±25 mmHg; proteinuria, 33Â±20 vs. 59Â±39 mg/day, both p < 0.05). Glomerular capillary density was increased, and less sclerosis was detected after healthy BMCs (both p < 0.05). Tubulointerstitial inflammation was also decreased after healthy BMCs. eGFP(+) cells were present in the glomeruli and peritubular capillaries of the remnant kidney in all BMC-treated rats. CKD BMCs also reduced SBP, proteinuria, glomerulosclerosis, and tubular atrophy versus vehicle in CKD rats. However, CKD BMC therapy was not functionally effective versus vehicle [GFR: 0.28Â±0.09 vs. 0.26Â±0.16 ml/min/100 g (NS), RPF: 1.15Â±0.36 vs. 0.78Â±0.44 ml/min/100 g (NS)], and failed to decrease tubulointerstitial inflammation and fibrosis. Single intrarenal injection of healthy BMCs in rats with established CKD slowed progression of the disease, associated with increased glomerular capillary density and less sclerosis, whereas injection of CKD BMCs was less effective.

Healthy bone marrow cells reduce progression of kidney failure better than CKD bone marrow cells in rats with established chronic kidney disease.

Insuffisance r&eacute;nale chronique (IRC) est un probl&egrave;me de sant&eacute; majeur. Nouvelles interventions &agrave; ralentir ou emp&ecirc;cher la progression de la maladie sont n&eacute;cessaires d&#39;urgence. Nous avons &eacute;tudi&eacute; les effets fonctionnels et structurels d&#39;une perfusion de sain et de cellules de moelle osseuse CKD (CR) dans un mod&egrave;le de rat de CKD &eacute;tabli. CKD a &eacute;t&eacute; induite par n&eacute;phrectomie 5/6 (SNX) chez les rats Lewis et progression de la maladie s&#39;est acc&eacute;l&eacute;r&eacute;e avec la L-NNA et r&eacute;gime contenant 6 % de NaCl. Six semaines apr&egrave;s SNX, CKD rats ont re&ccedil;u sain eGFP(+) CR, CR eGFP(+) CKD ou v&eacute;hicule par injection unique de l&#39;art&egrave;re r&eacute;nale. Des concentrations de r&eacute;f&eacute;rence en sant&eacute; &eacute;taient fonctionnellement efficaces 6 semaines apr&egrave;s l&#39;administration : taux de filtration glom&eacute;rulaire (GFR, clairance de l&#39;inuline) (0.48&plusmn;0.16 vs 0.26&plusmn;0.14 ml/min/100 g) et le d&eacute;bit plasmatique r&eacute;nal efficace (FPR ; D&eacute;gagement de PAH) (1.6&plusmn;0.40 vs 1.0&plusmn;0.62 ml/min/100 g) ont &eacute;t&eacute; plus &eacute;lev&eacute;s en BMC sain-par rapport aux rats trait&eacute;s au v&eacute;hicule (les deux p &lt; 0,05). Pression art&eacute;rielle systolique (pas) et une prot&eacute;inurie &eacute;taient inf&eacute;rieurs 5 semaines apr&egrave;s le traitement avec BMC sains versus v&eacute;hicule (SBP, 151&plusmn;13 vs 186&plusmn;25 mmHg, prot&eacute;inurie, 33&plusmn;20 vs 59&plusmn;39 mg/jour, les deux p &lt; 0,05). Densit&eacute; capillaire glom&eacute;rulaire augmente, et moins la scl&eacute;rose en plaques a &eacute;t&eacute; d&eacute;tect&eacute;e apr&egrave;s ca sains (les deux p &lt; 0,05). Inflammation tubulo-interstitielle a &eacute;t&eacute; &eacute;galement diminu&eacute;e apr&egrave;s les cellules saines CR. eGFP(+) &eacute;taient pr&eacute;sents dans les glom&eacute;rules et p&eacute;ritubulaire capillaires du rein reste dans tous les rats trait&eacute;s au BMC. CKD ca r&eacute;duit aussi SBP, prot&eacute;inurie, glom&eacute;ruloscl&eacute;rose et atrophie des tubes contre v&eacute;hicule chez les rats CKD. Th&eacute;rapie de CKD BMC n&#39;&eacute;tait cependant pas fonctionnellement efficace contre v&eacute;hicule [GFR : 0.28&plusmn;0.09 vs 0.26&plusmn;0.16 ml/min/100 g (NS), RPF : 1.15&plusmn;0.36 vs 0.78&plusmn;0.44 ml/min/100 g (NS)] et n&#39;a pas diminuer l&#39;inflammation tubulo-interstitielle et fibrose. Une seule injection intrar&eacute;nale de BMC saine chez les rats d&#39;IRC &eacute;tabli a ralenti la progression de la maladie, associ&eacute;e li&eacute;e la densit&eacute; capillaire glom&eacute;rulaire accrue et moins de scl&eacute;rose en plaques, alors que l&#39;injection de CKD CR &eacute;tait moins efficace.

Les cellules saines de la moelle osseuse r&eacute;duisent la progression de l&#39;insuffisance r&eacute;nale mieux que les cellules de moelle osseuse CKD chez les rats atteints d&#39;insuffisance r&eacute;nale chronique &eacute;tablis.

Malattia renale cronica (CKD) &egrave; un grave problema sanitario. Sono urgentemente necessari nuovi interventi per rallentare o prevenire la progressione della malattia. Abbiamo studiato gli effetti funzionali e strutturali dell&#39;infusione di sano e cellule di midollo osseo CKD (BMC) in un modello del ratto di CKD stabilito. CKD &egrave; stata indotta da 5/6 nefrectomia (SNX) nei ratti Lewis, e la progressione della malattia &egrave; stata accelerata con L-NNA e 6% NaCl dieta. Sei settimane dopo SNX, ratti CKD ricevuto BMC eGFP(+) sano, CKD eGFP(+) BMC o veicolo da iniezione singola arteria renale. BMC sani erano funzionalmente efficace 6 settimane dopo la somministrazione: tasso di filtrazione glomerulare (GFR; clearance inulina) (0.48&plusmn;0.16 vs 0.26&plusmn;0.14 ml/min/100 g) e il flusso di plasma efficace renale (RPF; PAH clearance) (1.6&plusmn;0.40 vs 1.0&plusmn;0.62 ml/min/100 g) sono stati superiori in BMC sano-contro ratti trattati con veicolo (entrambi p &lt; 0,05). Pressione arteriosa sistolica (SBP) e proteinuria erano inferiori 5 settimane dopo il trattamento con BMC sano contro il veicolo (SBP, 151&plusmn;13 vs 186&plusmn;25 mmHg; proteinuria, 33&plusmn;20 vs 59&plusmn;39 mg al giorno, entrambi p &lt; 0,05). Densit&agrave; capillare glomerulare &egrave; stato aumentato, e meno sclerosi &egrave; stata rilevata dopo sano BMC (entrambi p &lt; 0,05). Infiammazione di nefrite era anche diminuito dopo cellule sane BMC. eGFP(+) erano presenti nei glomeruli e peritubulare capillari del rene residuo in tutti i ratti trattati con BMC. CKD BMC ridotto anche SBP, proteinuria, glomerulosclerosi e atrofia tubulare contro veicolo nei ratti CKD. Tuttavia, la terapia CKD BMC non era funzionalmente efficacia contro veicoli [GFR: 0.28&plusmn;0.09 vs 0.26&plusmn;0.16 ml/min/100 g (NS), RPF: 1.15&plusmn;0.36 vs 0.78&plusmn;0.44 ml/min/100 g (NS)] e non &egrave; riuscito a diminuire l&#39;infiammazione nefrite e fibrosi. Singola iniezione intrarenale del BMC sano nei ratti con CKD stabilito ha rallentato la progressione della malattia, associata con maggiore densit&agrave; di capillari glomerulari e meno sclerosi, considerando che l&#39;iniezione di CKD BMC era meno efficace.

Le cellule del midollo osseo sano riducono la progressione della insufficienza renale meglio di cellule del midollo osseo CKD in topi con malattia renale cronica stabiliti.

Article	Year
The cardiorenal connection. Hypertension\| PubMed ID: 14967846	2004
The severe cardiorenal syndrome: 'Guyton revisited'. European heart journal\| PubMed ID: 15615794	2005
The cardiorenal syndrome a classification into 4 groups? Journal of the American College of Cardiology\| PubMed ID: 19358954	2009
Renal venous congestion and renal function in congestive heart failure. Journal of the American College of Cardiology\| PubMed ID: 19833266	2009
The nitric oxide donor molsidomine rescues cardiac function in rats with chronic kidney disease and cardiac dysfunction. American journal of physiology. Heart and circulatory physiology\| PubMed ID: 20852057	2010
Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. Circulation research\| PubMed ID: 21350212	2011
Subtotal nephrectomy plus coronary ligation leads to more pronounced damage in both organs than either nephrectomy or coronary ligation. American journal of physiology. Heart and circulatory physiology\| PubMed ID: 22140040	2012
HEALTHY BONE MARROW CELLS REDUCE PROGRESSION OF KIDNEY FAILURE BETTER THAN CKD BONE MARROW CELLS IN RATS WITH ESTABLISHED CHRONIC KIDNEY DISEASE. Cell transplantation\| PubMed ID: 22469231	2012
Target organ cross talk in cardiorenal syndrome: animal models. American journal of physiology. Renal physiology\| PubMed ID: 22914779	2012
Healthy bone marrow cells reduce progression of kidney failure better than CKD bone marrow cells in rats with established chronic kidney disease. Cell transplantation\| PubMed ID: 23231961	2012

Lennart G. Bongartz

Biography

JoVE Journal Publications

Other Publications