Role of angiotensin II on protein expression of renal nitric oxide synthase in unilateral ureteral obstructive rat.

Background: In the kidney, angiotensin II (ANG II) and nitric oxide (NO) can stimulate each other. Unilateral ureteral obstruction (UUO) activates both substances, where ANG II is stimulated first and NO is augmented later. Objective: Investigate the role of ANG II on renal nitric oxide synthase (NOS) protein expression in UUO. Methods: Male Wistar rats were divided into sham and UUO. The UUO rats were treated separately with water, angiotensin converting enzyme inhibitor (ACEI), or angiotensin receptor type 1 blocker (ARB) for one day before UUO and continuously for one or seven days after the operation. The endothelial NOS (eNOS) and inducible NOS (iNOS) protein expressions were examined in histology. Results: By immunohistochemistry, renal eNOS protein expression in the sham group showed staining in glomerulus and tubular epithelial cells in the cortex and medulla. UUO for one or seven days increased eNOS protein expression. ACEI or ARB reduced the heightened expression caused by UUO in 1-day group. However, in 7-day group, the elevated expression was maintained in the cortex, but was further increased in the medulla after ACEI or ARB administration. Both 1-day and 7-day UUO, with or without angiotensin blockade agents, caused no change in iNOS protein expression. One-day UUO resulted in mild tubular dilatation and cell infiltration. ACEI or ARB could attenuate structural alterations. The 7-day UUO rats demonstrated progressively morphological changes. ACEI was more effective than ARB in reducing tissue destruction. Conclusion: In UUO, angiotensin blockade could attenuate renal eNOS protein expression in 1-day UUO group but not in 7-day UUO animals. The inhibition of angiotensin system ameliorates nephropathy induced by UUO.

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.

Renoprotective effects of erythropoietin.

Background: Accumulating evidences during the past decade suggest that erythropoietin (EPO) may have many beneficial actions other than on erythropoiesis because many non-hematopoietic cells, including kidney cells, also express EPO receptors. Objective: To summarize evidences of the renoprotective effects of EPO and review the possible mechanisms of renoprotection provided by EPO. Results: Experimental studies have demonstrated the renoprotective effects of EPO in acute as well as chronic renal injury models. These renoprotective actions are likely to be mediated by several mechanisms, either directly or indirectly. However, EPO therapy is also associated with adverse effects. Conclusion: EPO is potentially a novel renoprotective drug. Clinical use of EPO for renoprotection could not be beneficial if adverse side effects of EPO have been overcome.

Lipid peroxidation and renal injury in renal ischemic reperfusion: effect ofangiotensin inhibition.

OBJECTIVES: To investigate the role of angiotensin inhibition on lipid peroxidation (LPO) and renal pathology in ischemic reperfusion (IR). MATERIAL AND METHOD: Male Wistar rats were subjected to 15-, 30-, 45- or 60- minutes ofrenal ischemia (I) by left renal artery occlusion. In the 30-minute I group, reperfusion (R) for I day (13,R) was performed in additional animals that had been treated with water, angiotensin converting enzyme inhibitor (ACE]; enalapril 5 mg/kg/d), or angiotensin receptor type 1 blocker (ARB; losartan 10 mg/kg/d) one day before I and were continued for 1 day after R. Renal tissue malondialdehyde (MDA), an indicator of LPO, was examined during I and IR periods. Renal pathology was also determined. RESULTS: During ischemia, renal tissue MDA levels were increased throughout the 60-minute ischemic period and was maximum at 30 minutes of ischemia (p < 0.01). Histological changes in 30-minutes I group showed slight tubular cell congestion and mild interstitial edema. One day after reperfusion, MDA levels were still elevated (p < 0. 01) when compared with sham. Progression of renal pathology was observed after I day of reperfusion. Both ACEI and ARB could attenuate the heightened MDA levels (p < 0.01). IR-induced renal injury was markedly diminished by administration ofACEI as well as by ARB. CONCLUSION: These results indicate that inhibition of angiotensin could reduce lipid peroxidation and ameliorate renal injury during IR condition.

Study of cyclosporine level at 2 hours after administration in preoperative kidney transplant recipients for prediction of postoperative optimal cyclosporine dose.

OBJECTIVE: Absorption profiling of cyclosporine is a current concept of drug monitoring. A single blood concentration measurement 2 hours after cyclosporine administration (C2) has been shown to be a good predictor of drug exposure and clinical outcome. The recommendation states that achieving the recommended target level of 1700 +/- 340 ng/ml within 3-5 days after renal transplantation is associated with a lower rate of acute rejection and nephrotoxicity. The high variation of pharmacokinetic profile and short limited time during early post-transplantation period make it hard to adjust the cyclosporine dose that can reach that target level on time. The present study was designed to be a method to predict the optimal pre-transplant CsA dose. MATERIAL AND METHOD: Eleven living-related kidney transplant recipients were recruited to receive cyclosporine and were monitored for C2 concentration during the 2 weeks before operation by the designed method. The pre-transplant empirical dose of 3.5 mg/kg/dose every 12 hours were assigned to all patients. The first predicted dose was estimated by using C2 concentration of 1,700 ng/mL. The first predicted dose was prescribed to the patients. The second predicted dose was estimated by using C2 concentration of the first predicted dose. All patients received the average of the first and the second predicted doses of cyclosporine within 12-24 hrs before transplantation and until the 3rd day after transplantation. RESULTS: Nine out of 11 patients (81.81%) reached the target C2 level on the 3rd day after transplantation without any serious side effect and complications. The most common side effect was nausea and a flushing sensation that usually abated with a later dose after transplantation. CONCLUSION: The early postoperative optimal cyclosporine dose can be effectively predicted by pre-transplant C2 measurement as conducted in the present study.

The combination of thrombotic microangiopathy and nodular sclerosis in light chain deposition disease.

The authors reported the first case of nodular glomerulosclerosis, mesangiolysis, and thrombotic microangiopathy in a 69-year-old Thai man with chronic glomerulopathy from light chain deposition disease associated with multiple myeloma and kappa monoclonal gammopathy. He presented with subacute onset of generalized edema, hypertension, and renal insufficiency. Blood examinations revealed kappa monoclonal gammopathy. The diagnosis of multiple myeloma was confirmed by bone marrow aspiration and biopsy. The renal pathologies demonstrated specific findings for light chain deposition disease which were type II nodular glomerulosclerosis, strongly PAS-stained tubular basement membrane, monotypic-kappa light chain deposition along tubular and glomerular basement membranes, and granular electron dense deposits in electron microscopy. However the authors also found the concomitant findings of mesangial and endothelial injuries which were mesangiolysis and thrombotic microangiopathy. Of interest, type II nodular sclerosis and thrombotic microangiopathy were caused by the same cell injury. These might shed new light on the pathogenesis of glomerular injury in monoclonal immunoglobulin deposition disease (MIDD).

Efficacy of cellulose triacetate dialyzer and polysulfone synthetic hemofilter for continuous venovenous hemofiltration in acute renal failure.

OBJECTIVE: To compare the clearance performances and biocompatibility between the modified cellulose membrane and the standard synthetic membrane in continuous renal replacement therapy (CRRT). MATERIAL AND METHOD: Seventeen patients with acute renal failure (ARF) were treated with separated continuous veno venous hemofiltration (CVVH) system conducted with the pre-dilution mode. The modified cellulose used was a Sureflux150E (cellulose triacetate) and the standard synthetic membranes used was an AV-400. Blood and replacement flow rate were kept at 100 and 20 mL/min, respectively. Ultrafiltraion rate was 1,200 mL/hr. Samplings of blood and ultrafiltrate were collected at baseline, 2, 8, 16, and 24 hr. RESULTS: Patients in both methods could similarly tolerate CRRT with only minor complications. Sureflux 150E and AV-400 provided comparable values of sieving coefficients and clearances of small solutes. The albumin loss in ultrafiltrate by Sureflux 150E was greater than AV-400. The values of life span and biocompatability of both hemofilters were not different. CONCLUSION: Because of the excellent efficacy and the much cheaper cost, the modified cellulose membrane could be an appropriate alternative to standard synthetic membrane in CRRT.

Accuracy of using 30-minute post-dialysis BUN to determine equilibrated Kt/V.

BACKGROUND: The equilibrated Kt/V (eKt/V), a clinical index of hemodialysis adequacy, can be calculated by several means. The commonly used methods are second generation of natural logarithm by Daugirdas and rate adjustment methods. However these two methods used immediate post-dialysis blood urea nitrogen (BUN) (C0). The authors investigated the accuracy of 30-minute post-dialysis BUN (C30), equilibrated BUN at the end of urea rebound time, to determine the eKt/V MATERIAL AND METHOD: We measured 7 values of eKt/V in 30 hemodialysis sessions by using the 5 following methods: 1). Empirical method (Emp) 2). Smye method (Sm) 3). Daugirdas method using C0 and C30 (Dau0, Dau30) 4). Rate adjustment method using C0 and C30 (Rate0, Rate30) 5). Double Pool urea kinetic model (DP), and compared with the gold standard values calculated by the modified Direct Dialysate Quantitative method (mDDQ). RESULTS: All patients had adequate hemodialysis with eKt/V (mDDQ) = 1.80 + 0.22. Compared with mDDQ, the median of absolute difference of eKt/V were Rate30 (0.10); Dau30 (0.11), Rate0 (0.11), Sm (0.11); Emp (0.13); DP (0.15); Dau0 (0.35) while the correlation coefficient (r2) were 0.926, 0.948, 0.785, 0.629, 0.551, 0.833,and 0.806 respectively. CONCLUSION: By using 30-minute post-dialysis BUN to calculate, the values of eKt/V by Daugirdas and rate adjustment methods were associated with better accuracy and correlation than immediate post-dialysis BUN. In the demand of the accurate eKt/V measurement, the Dau30 and Rate30 may be the suitable method to determine the eKt/V in clinical hemodialysis.

Update in pathophysiology and histopathology of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome in an adult worldwide. The prevalence of FSGS is estimated as being 20-30% in adults over the age of 15 years and slightly higher (30-35%) in the elderly (age > 60 years). The diagnosis solely relies on pathologic findings, which sclerosis involves some, but not all glomeruli (focal), and sclerosis affects a portion, but not the entire, glomerular tuft (segmental). The pathogenesis remains inconclusive but podocyte injury has been postulated. Even though steroid is the mainstay treatment, only 20-40% of patients are complete respond.

The effectiveness of on-line hemodiafiltration on beta-2 microglobulin clearance in end stage renal disease.

OBJECTIVE: To compare beta2-microglobulin (beta2M) clearance between on-line hemodiafiltration (HDF) and high flux hemodialysis (HFHD). MATERIAL AND METHOD: The total, convection/diffusion, and membrane adsorption components of beta2M clearance in 10 hemodialysis patients treated with on-line HDF at the replacement fluid rates of 75 (HDF75) and 125 (HDF125) mL/min, were determined and compared with HFHD. RESULTS: The total beta2M clearance in the HDF 125 group was significantly higher than the HDF75 group (124.5 +/- 4.4 vs 101.3 +/- 4.1 mL/min; p < 0.05); both values were much greater than the HFHD group (p < 0.01). The convection/diffusion was the major portion of total beta2M clearance in all three groups. The values of convection/diffusion and membrane adsorption in both HDF groups were about 2 and 3 times, respectively, of the HFHD group (p < 0.01). Both components of beta2M clearance in the HDF125 group did not statistically differ from the HDF75 group, however; the value of convection/diffusion clearance in HDF125 was more than in the HDF75 group. Regarding Kt/Vurea and phosphate clearance, there were no significant differences among the study groups. CONCLUSION: On-line HDF could provide more beta2M clearance than HFHD by increasing both the convection/ diffusion, and membrane adsorption clearances. HDF125 provided more total beta2M clearance than HDF75 from the convection/diffusion mechanism while the adsorptive mechanisms were equal.

Clinical characteristics and histopathological findings in 120 IgA nephropathy patients in Thailand.

The authors reviewed the clinical and pathological findings in 120 IgA-nephropathy (IgAN) patients diagnosed at King Chulalongkorn University Hospital from 1994 to 2005. The average age of the patients was 36 years. Male and female ratio was 1:1.2. Thirty percent of the patients had hypertension. Thirty-four percent of the patients had serum creatinine greater than 1.5 mg/dl and had urine protein greater than 3 g/day. The most common presentation was asymptomatic urinary abnormalities (43%) followed by nephrotic syndrome (36%). Of note, many of the presented patients had advanced pathological classification and high tubulointerstitial (TI) fibrotic score. The clinico-pathological correlation was found significantly between serum creatinine and degree of TI fibrotic score by univariate analyses. Compared to other reports from Asian countries, the presented population had many worse prognostic markers including a decline in renal function, advanced pathologic findings, and high TI fibrotic scores. Further study on prognosis in Thai patients should be performed to help decision making in management of IgAN patients.

Alleviation of renal and pulmonary injury by immunomodulation in leptospirosis: hamster model.

OBJECTIVE: Severe leptospirosis manifestations include acute renal failure, caused by acute interstitial nephritis and pulmonary hemorrohage. Spirochete invasion and toxicity of outer membrane cause robust inflammatory host responses. These responses lead to the generation of cytokines, chemokines, and inflammatory cell infiltrations which result in severe organ dysfunctions. The immunomodulation by the modulation of host immune response may alleviate the renal and pulmonary injury. The authors determined whether the current immunosuppressive agents could alleviate the inflammation and minimize the organ injury in hamster model. MATERIAL AND METHOD: The animal experiments were conducted with the approval of The Ethical Research Committee of Chulalongkorn University Hospital. The leptospira interrogan serovar pyrogenese was isolated from a wild rat. The spirochete was grown in Fletcher's semisolid media and after subcultures were transferred to the Fletcher's liquid media. An amount of 0.5 ml of the spirochete culture media containing 1 x 10(8) leptospires/ml was intraperitoneally injected to golden Syrian hamsters (Mesocrietus auratus), age 4-6 weeks, weighing 60-80 grams. The hamsters were randomed into 5 groups (n = 4 in each group) namely, 1) Normal group (Control group), 2) Leptospira group, 3) CsA group (leptospira with cyclosporine feeding, 100 mg/kg/ day), 4) Rapa group (leptospira with rapamicin feeding, 0.6 mg/kg/day), and 5) Irra group (leptospira with irradiation). Cyclosporine and rapamicin were started at day 0 after the spirochete injection. Gamma ray dose 200 cGy was irradiated to the hamster 3 days before the spirochete inoculation. The animals were autopsied or euthanized if expired or at day 5 post inoculation. The blood samples for BUN, and creatinine were drawn before the inoculation and at autopsy or euthanasia. RESULTS: The inoculation of L Interrogan 0.5 ml (1 x 10(8) leptospires/ml) without immunomodulation cause mortality of all animals at day 4 or day 5 post inoculation. The blood chemistry showed acute severe azotemia. The autopsy findings revealed severe interstitial nephritis and severe pulmonary hemorrhage. The hamsters in the Rapa group had only minimal pulmonary hemorrhage and minimal focal interstitial inflammation of kidney. There were cytoadherance of inflammatory cells to the endothelial cells in lungs and kidneys without the intrusion into the interstitium. The blood chemistry in Rapa group showed mild elevation of BUN and Cr. The immunomodulation by cyclosporine and irradiation did not alleviate the disease. On the contrary, cyclosporine and irradiation caused more severe histopathology. CONCLUSION: The immunomodulation by rapamicin in leptospirosis in hamsters could alleviate the kidney and pulmonary injuries. The up-regulation of IL-2 in peripheral blood lymphocytes did not result in the kidney and pulmonary injuries.

Effectiveness of oral route isosorbide 5-mononitrate on peritoneal solute and fluid transports in CAPD patients.

BACKGROUND: Addition of sodium nitroprusside (NaNTP), a nitric oxide (NO) donor to peritoneal solution could enlarge the effective peritoneal surface area and the peritoneal pore size. This would be leading to increased clearance of all solutes. Generalized clinical usage of NaNTP in CAPD patients however is not practical because it has a very short half-life and needs a specific route of administration. Organic nitrate, another NO donor, has a longer half-life and could be more easily absorbed via many routes. OBJECTIVE: The present study was conducted to determine the effect and mechanism of oral active nitrate (isosorbide 5-mononitrate: ISMN) on solute andfluid transports in stable CAPD patients. MATERIAL AND METHOD: A prospective randomized placebo control with a crossover study was performed in nine stable CAPD patients. In group I (n = 4), the treatment included 1) oral ISMN at the dose of 20 mg bid for 5 days 2) wash out period for 7 days, and 3) placebo for 5 days. In group 2 (n = 5), the treatment regimens were placebo, wash out, and ISMN periods. RESULTS: The MTACs of low molecular weight (LMW) solutes in the ISMN period were greater than the placebo period: median urea, 16.7 vs 13.8 ml/min; creatinine (Cr), 7.9 vs 6.9 ml/min; and urate, 6.1 vs 5.5 ml/min (p < 0.05 for all except MTAC of urea). Administration of ISMN could also enhance the clearances of high molecular weight (HMW) solute with a magnitude of increase as follows: 10% for beta2-microglobulin, 50% for albumin, and 15% for immunoglobulin G (p < 0.05 for all). However, the values of restrictive coefficient of LMW as well as HMW solutes of both groups were not different, indicating that the increased solute transports are not due to alteration in the peritoneal membrane permeability. Despite the increased peritoneal solute clearance, net ultrafiltration (UF) was unchanged after drug administration, 110 (ISMN group) vs 120 ml (placebo group), (NS). CONCLUSION: ISMN has a similar effect as NaNTP in enhancing peritoneal clearances of both LMW and HMW solutes. The effect of ISMN, however, is mediated only via expansion of peritoneal surface area without significant change in pore size. As such, administration of oral ISMN to stable CAPD patients would be practically beneficial in enhancing the achievement of target solute clearances suggested by NKF- DOQI Guidelines.

Hepatitis-B virus-associated nephropathies in adults: a clinical study in Thailand.

Hepatitis B virus (HBV)-associated glomerulonephropathy (HBV-GN) has been increasingly reported, especially in adults. In the present study, the authors investigated the clinical and histopathology features of patients who suspected HBV-GN in 24 patients and age ranging from 23 to 74 years (mean 43 years). Asymptomatic hematuria was the most common presentation (54%); followed by edema and hypertension at equal percentages of 50%. The nephrotic syndrome was presented in 43%, the nephrito-nephrotic syndrome in 3.5%. Clinically suspected rapidly progressive GN was found in 14%. Renal insufficiency was determined in 30%. The most common pathologic finding was IgA nephropathy (IgAN 29%), followed by membranous nephropathy (21%), focal segmental glomerulo sclerosis (FSGS 11%), membranoproliferative GN (11%), post-infectious GN (11%). Liver disease activity also tended to be mild or had no symptoms of hepatitis. The authors remission rates both complete and partial were 75% (higher than the usual report), notwithstanding treatment. The authors achieved a sustained complete remission in half of the patients (3 in 6 cases) treated with steroid alone and 2 out of 7 cases (28.6%) treated with anti-viral therapy. Spontaneous remission was demonstrated in 2 (1 with IgAN + FSGS, and 1 with post infectious GN) out of 6 patients (33.3%). None of the patients in both treatment groups turned to ESRD that occurred in 2 cases receiving non-specific treatment. Of note, all of the patients who received anti-viral therapy or corticosteroid and had complete follow up were in remission either complete or partial.

The effect of angiotensin II receptor blocker on peritoneal membrane transports in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: The objective of this study was to examine the effects of angiotensin II receptor blocker (ARB), used as an antihypertensive medication, on peritoneal membrane transporters in continuous ambulatory peritoneal dialysis (CAPD) patients. MATERIAL AND METHOD: Prospective and cross-over experimental study of peritoneal membrane transporters was conducted in 7 CAPD patients with hypertension. All previous antihypertensive drugs had been replaced by candesartan at the dose of 8-16 mg/day to control blood pressure below 140/90 mmHg. Hydralazine, which has no effect on peritoneal membrane transports, was added if the target blood pressure was not achieved. All patients had received candesartan for 12 weeks, then, were retreated with the previous antihypertensive drugs for another 6-week period. The modified peritoneal function tests assessing peritoneal membrane transports were performed at 1) baseline, 2) 6 weeks, 3) 12 weeks following candesartan treatment, and 4) 6 weeks after candesartan withdrawal. RESULTS: The blood pressure target was achieved in all patients and was not different among the 4 periods. The albumin clearance and 4-hour albumin loss were significantly decreased following candesartan treatment (p < 0.05). Both values returned to the high baseline levels after 6 weeks of candesartan withdrawal. There were no significant changes in net ultrafiltration and various small and large solute transports. No adverse effects, including hyperkalemia or increased erythropoietin dosage, had been observed. CONCLUSION: In hypertensive CAPD patients, candesartan could provide nutritional benefit by attenuating peritoneal loss of albumin and provides an effective antihypertensive action. Furthermore, candesartan does not impair other solute transports and net ultrafiltration.

The clinicopathology and outcome of post-infectious glomerulonephritis: experience in 36 adults.

Post-infectious glomerulonephritis is one of the most common causes of acute glomerulonephritis. A retrospective study of post-infectious glomerulonephritis at King Chulalongkorn Memorial Hospital, Thailand was performed from January 1999 to December 2005. Among thirty six patients, eight cases were post-streptococcal glomerulonephritis and twenty eight cases were post non-streptococcal Glomerulo Nephritis (GN). Most cases present with edema, hypertension, gross hematuria and nephrotic-range proteinuria. C3 and CH50 commonly were low. Post-streptococcal glomerulonephritis had more aggressive pathology compared to the others. However the long term outcome was excellent. In the present study the authors found ESRD in only 14.3% (4 out of 28 cases) that reflects the excellent prognosis of post-infectious glomerulonephritis. Of interest, all of the ESRD patients were caused by post non-Streptococcal GN. Even though, no statistic was achieved; it might reflect the aggressiveness of non-Streptococcal pathogen.

A rare case of chylous ascites and chyluria in an adult nephrotic syndrome with focal segmental glomerulosclerosis.

The authors report the first case of chylous ascites and chyluria in a 65-year-old Thai women with nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS), tip variant. She presented with generalized edema and abdominal discomfort. Abdominal paracentesis revealed milky white fluid. Chylous ascites was confirmed. Abdominal and thoracic computed tomography did not show any cause of chylous ascites and chyluruia. Lymphoscintigraphy could not demonstrate lymph flow obstruction and connection between lymphatic pathway and KUB system. Those could have explained the chylous ascites or chyluria. Hypoalbuminemia-induced bowel edema may predispose to change the permeability of mucosal or serosal lymphatics. This could result in chylous ascites but the cause of chyluria could not be determined in this case.

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.

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.

Pioglitazone reduces urinary protein and urinary transforming growth factor-beta excretion in patients with type 2 diabetes and overt nephropathy.

OBJECTIVE: Increased urinary excretion of protein and transforming growth factor-beta (TGF-beta) are associated with progression of diabetic nephropathy (DN). Thiazolidinediones (TZD) could reduce urinary protein excretion in patients with microalbuminuric DN. There is little data of patients with macroalbuminuric DN. Also, there are no available clinical data regarding the effect of TZD on TGF-beta and type IV collagen in clinical DN. The present study was carried out to evaluate the effect of pioglitazone (PGZ), a member of TZD, on urinary protein, urinary TGF-beta, and urinary type IV collagen excretion in type 2 diabetic patients with macroalbuminuric DN. MATERIAL AND METHOD: Forty patients with type 2 diabetes and overt nephropathy, proteinuria more than 500 mg/day, were randomly assigned to receive PGZ (30 mg/day, n = 24) or placebo (control group, n = 16), for 12 weeks. Blood pressure, plasma glucose, glycated hemoglobin, lipid profile, 24-hour proteinuria, urinary TGF-beta and urinary type IV collagen were determined and compared. RESULTS: Glycemic control and blood pressure in both groups were not significant different. At baseline, the levels of proteinuria, urinary TGF-beta, and type IV collagen were not significant different between both groups. The geometric mean of urinary protein excretion in the PGZ group was progressively reduced from 1.64 to 0.98 gram/day (g/d), or 40.1% decrease which was significantly different (p < 0.05) from the 4.3% increase (from 1.72 to 1.80 g/d) in the control group. Urinary TGF-beta excretion in the PGZ group was decreased by 47.8% which significantly differed from the 59.7% increase in the control group (p < 0.05). Urinary type IV collagen levels in the PGZ group were decreased by 35% which was slightly, but not significantly, different from the 51.6% elevation in the control group (p = 0.06). CONCLUSION: Besides the effectiveness in blood sugar control, pioglitazone could salutarily reduce proteinuria and synthesis of TGF-beta as well as type IV collagen. These beneficial effects of pioglitazone on diabetic nephropathy are comparable to angiotensin converting enzyme inhibitors and angiotensin receptor blockers