The critical role of tubulointerstitium in renal disease progression.

Background: Recent works have demonstrated that, regardless of the primary causes, tubulointerstitial (TI) fibrosis is the major cause of progression of renal failure. Objective: To summarize the mechanisms of progression and regression of TI damage. Results: Experimental studies have shown that there are three common processes of progressive TI damage: injury, inflammation, and fibrosis. Renin angiotensin system (RAS) blocking agents could substantially decrease these lesions. Conclusion: The fulcrum of the balance between progression and regression of TI fibrosis remains to be elucidated but would be related to the activation of RAS.

Target quantity for twice-a-week hemodialysis: the EKR (equivalent renal urea clearance) approach.

OBJECTIVE: The targets of dialysis per session, in terms of Kt/V and URR are well established for thrice-a-week hemodialysis (HD). The target values of these parameters could not be applied for the patients undergoing twice-a-week HD, which is performed in several developing countries. The equivalent renal urea clearance EKR (EKR [mL/min) = G (mg/min)/TAC (mg/mL)], which measures urea clearance in a continuous fashion, has been used in comparing amount of dialysis among the different modalities. For any chronic dialysis regimens the target EKRc, which was normalized to urea volume of distribution of 40 L, would be above 13 mL/min. Therefore, there is no data available regarding Kt/V, URR, and EKRc for twice-a-week HD. MATERIAL AND METHOD: The EKRc of 26 Thai patients treated with twice-a-week high flux HD were measured monthly for 12 months. The Kt/V, URR, and serum albumin were also measured monthly. RESULTS: Overall, the mean EKRc of 294 patient-month analysis was 11.68 +/- 0.16 mL/min. Monthly EKRc had a high correlation to Kt/V (r = 0.80) and URR (r = 0.82). When serum albumin was employed as a surrogate marker for treatment failure, ROC analysis revealed that EKRc above 13 mL/min had 90% and 100% probabilities to maintain monthly and 12-month serum albumin levels above 4 gm/dL, respectively. To obtain the target EKRc above 13 mL/min at 90 and 95% confidence, the values of Kt/V per session were 2.11 and 2.25, respectively while those of URR were 82.89 and 84.52%, respectively. CONCLUSION: For twice-a-week HD, to have the EKRc level above 13 mL/min, at 95% confidence, the Kt/V should exceed 2.2 and the URR should exceed 85% per session.

Citrate attenuates tubulointerstitial fibrosis in 5/6 nephrectomized rats by decreasing transforming growth factor-beta1.

OBJECTIVE: Tubulointerstitial fibrosis plays an essential role in progression to end stage renal disease (ESRD) in various chronic renal failure (CRF) models including the 5/6 nephrectomy (5/6). The present study examines the renoprotective effect of citrate in the renal ablative model that is quite similar to CRF in human. MATERIAL AND METHOD: Male Wistar rats underwent 5/6 and were fed with tap water (5/6tap) or tap water containing 67 mEq/L citrate solution (5/6cit). Sham-operated rats (S) were divided into Stap and Scit groups. Renal function, renal histopathology, renal alpha-Smooth muscle actin (SMA), and renal transforming growth factor (TGF)-beta1 were determined immediately and at the 8th week after operation. RESULTS: Following the surgery, the values of glomerular filtration rate (GFR) in the 5/6tap and the 5/6cit groups were 2.39 +/- 0.25 and 2.35 +/- 0.25 (mL/kg/min), respectively, both were significantly lower than sham groups (p < 0.05). At the eighth week, the 5/6tap group had progressively decreased GFR and had higher fibrosis score, increased alpha-SMA positive cells, and renal tissue TGF- beta1 when compared with the sham groups. The 5/ 6cit group, when compared with the 5/6tap group, had higher GFR (2.51 +/- 0.22 vs 1.17 +/- 0.33 mL/kg/min; p < 0.05), lower fibrosis score (1.83 +/- 0.88 vs 3.0 +/- 0.4, p < 0.001), lower alpha-SMA activity (159 +/- 2.9 vs 187 +/- 12.3 cells per 1000 interstitial cells, p < 0.05), and lower renal TGF-beta1 levels (1771.3 +/- 239.5 vs 4716.9 +/- 871.2 pg/mg protein, p < 0.005). CONCLUSION: As such, in 5/6 nephrectomized rats, citrate therapy for eight weeks could decrease tubulointerstitial fibrosis mainly by reducing the heightened renal TGF-beta1 levels and additionally by attenuating the increased myofibroblast activity.