Impact of patterns of proteinuria on renal allograft function and survival: a prospective cohort study.

BACKGROUND: Proteinuria is an important complication in renal transplant recipients. The aim of this prospective study was to evaluate the long-term impact of transplant proteinuria patterns on allograft function and survival. METHODS: We analyzed urinary protein of a cohort of 83 renal transplants with proteinuria ≥0.5 g/d by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and radial immunogel diffusion assay. After initial stratification and analysis, the cohort was followed up for 16 yr. The graft outcome and survival were analyzed using Cox regression model to determine their association with different patterns of initial transplant proteinuria. RESULTS: Group with predominantly glomerular (middle- and high-molecular-weight with or without low-molecular-weight) proteinuria (61%) had higher serum creatinine (p < 0.001) than the group with predominantly tubular (low-molecular-weight) proteinuria (39%). The incidences of chronic graft dysfunction and graft loss had increased in the glomerular proteinuria group (p < 0.001, hazard ratio 3.6, 95% confidence interval 1.7-7.5 and p < 0.001, hazard ratio 4.9, 95% confidence interval 1.9-12.1, respectively). Patient death did not differ (p = 0.434, hazard ratio 1.5, 95% confidence interval 0.5-4.5). CONCLUSION: Proteinuria in renal transplants can be differentiated into glomerular and tubular types based on molecular weight. Glomerular proteinuria is associated with significant increase in graft dysfunction and graft loss.

The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades.

This review of 2,586 renal biopsies over the past 3 decades in Singapore documents the changing pattern of glomerulonephritis (GN) from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative glomerulonephritis was the most common form of primary GN, just as it was in the surrounding Asian countries. In the 2nd decade, the prevalence of mesangial proliferative GN decreased with a rise in membranous, GN which is also seen in China and Thailand. In the 3rd decade, there was a dramatic increase in focal sclerosing glomerulosclerosis. This increase reflects aging and obesity in keeping with more developed countries like Australia, India, Thailand and the United States of America. IgA nephritis remains the most common GN. Apart from the geographical influence, other socioeconomic factors play a significant role in the evolution of the renal biopsy pattern. Mesangial proliferative GN remains prevalent in many Asian countries, but in Singapore the prevalence is decreasing just as it is in Japan, Korea and Malaysia. Worldwide, the prevalence of focal sclerosing glomerulosclerosis continues to increase in many countries.

Beneficial effects of high-dose losartan in IgA nephritis.

AIM: Several short-term studies have reported the efficacy of high-dose ARB in reducing proteinuria in patients with diabetic nephropathy. The benefits of long-term high-dose ARB losartan in IgA nephritis have not been explored. METHOD: This was a 6-year randomized trial in 207 patients with IgA nephritis comparing high-dose ARB (losartan 200 mg/day) with normal dose ARB (losartan 100 mg/day), normal dose ACEI (20 mg/day) and low-dose ACEI (10 mg/day). Multivariate ANOVA was used to test the effect of drug treatment on both eGFR and total urinary protein (TUP). RESULTS: Comparing patients on high-dose ARB (n = 63) with those on normal dose ARB (n = 43), normal dose ACEI (n = 61) and low-dose ACEI (n = 40), patients on high Dose ARB had significantly higher eGFR (p < 0.0005) and lower proteinuria (p < 0.005) at the end of the study. The loss in eGFR was 0.7 ml/min/year for high-dose ARB compared to 3.2 - 3.5 ml/ min/year for the other 3 groups (p = 0.0005). There were more patients on high-dose ARB with improvement in eGFR compared to other 3 groups (p < 0.001). CONCLUSION: Data from this study suggest that high-dose ARB therapy is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI. In Year 5, patients on high-dose ARB had a gain in eGFR suggesting that there is possibility of recovery of renal function in these patients on long-term high-dose therapy.

Long term outcome of renal allografts in patients with immunoglobulin A nephropathy.

Recurrent glomerular disease is an important cause of late allograft loss in renal transplant recipients. Immunoglobulin A nephropathy (IgAN) is a leading cause of end-stage renal disease (ESRD) worldwide and its recurrence has been reported in allografts. The present study examined outcomes following renal transplantation (RTX) in 101 patients with ESRD due to biopsy-proven IgAN, in comparison to non-IgA patients, and evaluated the incidence of recurrence. The study population (mean age 34.8 +/- 7.7 years; males 62.2%; Chinese 88.3%) underwent RTX under CsA immunosuppression between November 1984 and December 2004; as two patients underwent retransplantation during the study period, 103 allografts (56.3% cadaveric) were included for retrospective analysis. At time of analysis on 1 January 2005, 78 (75.7%) renal allografts (IgAN RTX) were functioning, of which 51 (49.5%) had normal serum creatinine, 27 (26.2%) had chronic allograft dysfunction, while 25 had graft losses, either due to patient death with functioning grafts (5.8%) or withdrawal to dialysis (18.5%). Persistent microscopic haematuria, not attributable to other causes or proteinuria > 1 g/day occurred in 42.7% and 13.6% of allografts respectively. Of 29 allografts biopsied for evaluation of proteinuria and/or renal dysfunction post-RTX, 8 (27.6%) had IgAN (overall histological recurrence, 7.8%). Of these, three had graft loss due to recurrent IgAN, three had elevated serum creatinine, while two had normal serum creatinine. Overall five and ten year patient survivals for IgAN RTX were 95.3% and 82.2%, and five and ten year actuarial graft survivals were 82.3% and 67.8% respectively. Five and ten year patient and graft survivals for IgAN RTX were not significantly different from that for non-IgAN RTX. In summary, RTX patients with IgAN have a low incidence of documented histological recurrence and recurrence contributing to graft loss occurs in only 2.9%. These results suggest that RTX is an excellent modality of renal replacement therapy in this population.

ATRA therapy restores normal renal function and renal reserve and prevents renal failure.

This article presents clinical data which suggest that the current dosage of losartan 50 to 100 mg/day may not be the optimum in many cases, especially if used as monotherapy in the treatment of proteinuria and we may have to increase to 200 mg/day. However, about 30% of patients cannot take angiotensin-converting enzyme inhibitor (ACEI) because of the side effect of cough. To potentiate the anti-proteinuric effect of losartan, especially for patients who do not adhere to a low salt diet, a 12.5-mg dose of hydro-chlorothiazide may further decrease proteinuria. The main message of this article is that we would have to, in many instances, increase the dose of losartan to a minimum of 100 mg/day or 100 mg twice a day for some patients for optimal therapy. The second message is to monitor the creatinine clearance test (CCT) and to start therapy when CCT is reduced and not wait for serum creatinine to rise to abnormal levels (renal impairment) before starting therapy. The first group involves half a dozen patients with hypertension but no proteinuria. Therapy with losartan is shown to improve the renal function. This data suggest that losartan, apart from its use in reduction of proteinuria, can be used in patients with mild renal impairment without proteinuria to reverse the mild renal impairment and preserve renal function. The second group deals with 3 patients with low creatinine clearance. After a followup period of an average of 3 years, they all developed renal impairment. In another 6 patients, the data suggest that we should perhaps treat patients with low CCT as soon as possible and with dose ranging from 100 to 200 mg/day if necessary, to derive maximum beneficial effect. The third group highlights 5 patients with high CCT due to glomerular hyperfiltration. With time, the high CCT decreases and renal impairment sets in. The data suggest that patients with high CCT should be treated early to prevent renal impairment. The fourth group illustrates 6 patients where their proteinuria was markedly reduced with the increase of losartan from 100 mg/day to 200 mg/day, suggesting that losartan 200 mg/day is probably the optimum dose. In conclusion, apart from its traditional usage in reduction of proteinuria to retard progression to renal failure, the data suggest that losartan is also indicated in patients with renal impairment in the absence of proteinuria; patients with low CCT, patients with high CCT and patients who do not respond to a dosage of 100 mg/day should have the dosage increased to 100 mg twice daily to increase efficacy of losartan. It is hoped that with these new and earlier indications as well as increased dosage of losartan starting with 100 mg, whenever possible, and increasing to 200 mg/day, if there is no response, we can prevent more patients from developing renal failure. Based on these observations, further randomised controlled trials should be designed to address these issues.

Action of dipyridamole and warfarin on growth of human endothelial cells cultured in serum-free media.

OBJECTIVE: To study the anti-proliferative effect of Dipyridamole (anti-platelet), Dipyridamole with Warfarin, and Warfarin (anticoagulant) alone, in human endothelial cells in vitro. DESIGN AND METHODS: Human endothelial cells were harvested from umbilical cords. Primary cultures were usually successful. However, subculture yields were usually contaminated with smooth muscle cells. We have developed an improved method for the isolation of endothelial cells by using Collagenase II, coating the culture flask with fibronectin and using serum-free media. The endothelial cells were characterised by anti-PECAM-1/PE (CD31) using Flow Cytometry with viability of 95% after trypsinization with 0.05% Trypsin and 1 mM EDTA. Growth and proliferation studies were performed in vitro in the presence of 5 microM Dipyridamole, 5 microM Dipyridamole with 5 microM Warfarin, 5 microM Warfarin alone by cell counts, (3)H-thymidine and (3)H-leucine incorporation. RESULTS: The incorporation of (3)H-Leucine at day 6 in each test condition revealed no significant change. Control 12678 +/- 2968 CPM, Dipyridamole 8698 +/- 189 CPM, Dipyridamole and Warfarin 7541 +/- 413 CPM, and Warfarin alone 10711 +/- 732 CPM. With the incorporation of (3)H-Thymidine, Dipyridamole alone as well as Dipyridamole with Warfarin reduced the basal proliferation rates significantly when compared to controls. Control 14355 +/- 4441 CPM, Dipyridamole 1100 +/- 152 CPM (p<0.05), Dipyridamole with Warfarin 1092 +/- 272 CPM (p<0.05). Warfarin alone did not reduce proliferation significantly 12870 +/- 2677 CPM (NS). CONCLUSIONS: We have developed a method to isolate pure endothelial cells from human umbilical cords using Serum-Free Media (SFM). EC with high purity was characterised by anti-PECAM-1/PE (CD31) using Flow Cytometry. Dipyridamole at a concentration of 5 microM inhibited the proliferation of endothelial cells at day 6 by 93%. These techniques can be used for routine analysis and proliferation studies.

Antithrombin III in renal transplant recipients.

Antithrombin III (AT III) is increased in situations where there is increased platelet turnover. Plasma AT III levels measured in 39 renal transplant recipients were significantly higher than in 20 healthy subjects (p less than 0.001) and 20 patient controls (p less than 0.025). AT III levels were significantly correlated with the patients' platelet counts (r = 0.4, p less than 0.02). Transplant patients with less than 1 year follow up had significantly higher AT III levels than patients with more than 1 year follow up (p less than 0.01). All 5 patients with transplant rejection in the study had elevated plasma AT III levels. The data suggest that elevation of plasma AT III may be related to graft rejection.

Antithrombin III in mesangial IgA nephritis.

Plasma Antithrombin III (A T III) was measured in 97 patients with IgA nephritis, 30 patients with non IgA idiopathic mesangial proliferative glomerulonephritis and 40 healthy subjects. The mean plasma A T III levels in the patients with IgA nephritis (105 +/- 10%) was significantly higher than those of normal controls (96 +/- 5%) (p less than 0.0005). The mean plasma A T III levels in the patients with non IgA nephritis (101 +/- 10%) was not different from those of the normal controls or the patients with IgA nephritis. A T III levels were significantly correlated with proteinuria (p less than 0.0001), segmental sclerosis (p less than 0.001), crescents (p less than 0.01), medial hypertrophy (p less than 0.001) and intensity of IgA staining on IMF (p less than 0.02). Patients with IgA nephritis with raised A T III levels had significantly more proteinuria (p less than 0.003), more segmental sclerosis (p less than 0.007) as well as a greater intensity of IgA staining on IMF (p less than 0.02) when compared to patients with normal A T III levels. The data suggest that raised plasma A T III levels may serve as a prognostic marker in IgA nephritis.

Pattern of proteinuria in IgA nephritis by SDS-PAGE: clinical significance.

Of sixty patients with IgA nephritis, none had CRF at first examination, 13 developed CRF with creatinine above 1.6 mg/dl within 6 years. Among these patients who had analysis of proteinuria by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), 31 patients had middle molecular weight (MMW) proteinuria alone (pattern 1), 10 had MMW and Low MW (LMW) or tubular proteinuria (pattern 2), 10 had high MW (HMW) and MMW proteinuria (Pattern 3) and 9 had HMW, MMW and LMW proteinuria (Pattern 4). At the end of a follow up period of 6 years (1983-1989) patients with mixed proteinuria had a higher incidence of chronic renal failure (CRF), 11/29 (38%) compared to those with pattern 1 proteinuria, 2/31 (6%) (chi 2 = 8.7, p less than 0.005). Based on the glomerular selectivity index (GSI), 19 patients had nonselective proteinuria but they did not have a higher incidence of CRF. By the selectivity index (SI), 18 patients had nonselective proteinuria and they showed a significantly higher incidence of CRF. Compared to the 41 patients who did not have LMW proteinuria, 19 patients with LMW proteinuria had more severe proteinuria. After a follow-up period of 6 years, patients with LMW proteinuria had a higher incidence of CRF (10% versus 47%, p less than 0.001). The presence of LMW proteinuria indicates a less favourable outcome and the pattern of proteinuria as assessed by the SDS-PAGE appears to be a better prognostic index in IgA nephritis than the SI and the GSI.

Effects of triple therapy in IgA nephritis: a follow-up study 5 years later.

This study is a 5-year post trial assessment of patients with IgA nephritis who entered a 3-year prospective controlled trial of cyclophosphamide, dipyridamole (D) and low-dose warfarin (W). Patients entered the trial from 1979 to 1981 and the trial ended in 1984 with those in the treatment group having more stable renal function and less proteinuria compared to the control group. Present reassessment of the patients in 1989 showed no difference in the renal function between those in the treatment group (n = 27) and the control group (n = 21). 6 patients in the treatment group and 7 in the control group were in ESRF. At the conclusion of the trial in 1984, among the 27 patients in the original treatment group, 13 patients elected to continue with D + W while the other 14 patients chose to cease therapy and therefore served as the new control group. 5 years later, renal function in the new treatment group (n = 13) was significantly stable compared to the new control group (n = 14), (serum creatinine 1.4 +/- 0.7 versus 4.4 +/- 3.2 mg/dl, p less than 0.01). Furthermore, all the 6 patients with ESRF in the original treatment group of 27 patients were from the new control group (n = 14) where treatment with D + W had been ceased. None of the patients still on D + W are in ESRF.

Triamterene-induced crystalluria and cylinduria: clinical and experimental studies.

We examined the occurrence of crystals and casts in the urine of healthy subjects after administration of triamterene and the site of crystal formation in experimental animals. Twenty out of twenty healthy subjects had abundant triamterene crystals and casts in acid urine after receiving a single 100 mg dose. Casts were present in the urine from 2-11 hours after administration of the diuretic. Cast formation occurred in acidic urine and was prevented by alkalinization of the urine with potassium citrate. Animal studies showed that crystallization and cast formation occurred in the medullary and papillary collecting ducts of the rat kidney. These findings provide a possible explanation for the reported nephrotoxicity of triamterene, particularly when given to patients who are receiving non-steroidal anti-inflammatory agents.

The changing pattern of glomerulonephritis in Singapore over the past two decades.

This study reviews the pattern of glomerulonephritis (GN) in Singapore over the past 2 decades. In the earlier decade the pattern was typical of most Asian countries with mesangial proliferative GN (Mes GN) (56%) as the most common form of primary GN including the nephrotic syndrome (40%). In the 2nd decade the pattern undergoes a change. Though Mes GN is the commonest primary GN (42%), the commonest form of nephrotic syndrome is now minimal change disease (30%) with Mes GN decreasing to 25% among all primary nephrotic syndromes. Both minimal change and focal global sclerosis account for 50% of steroid/cyclophosphamide responsive GN today. Membranous GN though still uncommon, has increased from 3% (1st decade) to 6% (2nd decade) (p < 0.01). IgA nephritis is still the commonest primary GN occurring in Singapore (42% of all primary GN in the 1st decade and 45% in the 2nd decade). The present pattern of GN in Singapore, though, still predominantly Asian with the preponderance of mesangial proliferative GN with a relatively low incidence of membranous GN contrasts with the pattern in the West where membranous GN is the commonest form of primary GN. Even the incidence of FSGS has not increased as in the West where there is a rising incidence. The underlying basis for most GN in Singapore as in other Asian countries and elsewhere is antigen-driven: infective antigen as well as food or other allergens.

Beta-thromboglobulin and platelet aggregates in glomerulonephritis.

Circulating platelet aggregate ratios (CPAR) and plasma beta-thromboglobulin (B-TG) concentrations were determined in 53 patients with chronic progressive glomerulonephritis [mesangiocapillary glomerulonephritis (15) and focal and segmental hyalinosis and sclerosis (38)] and compared with those from both normal subjects and patients with no evidence of renal disease. The mean B-TG concentration was higher in patient controls [32.6 +/- 6.2 ng/ml (SEM)] than in normal subjects [19.0 +/- 2.0 ng/ml (SEM)] but this did not reach significance (P < 0.10 > 0.05). Nephritic patients had markedly elevated levels [49.8 +/- 4.0 ng/ml (SEM)], but B-TG was significantly correlated with renal impairment. Elevated B-TG levels in patients with nephritis may thus reflect renal impairment or ill-health. The mean CPAR of the nephritic patients [0.75 +/- 0.02 (SEM)] was lower than that of both normal [0.86 +/- 0.03 (SEM), P < 0.001] and patient controls [0.87 +/- 0.02 (SEM), P < 0.001]. CPAR was not correlated with renal function or platelet concentration. Low CPAR in nephritic subjects provides further evidence for in-vivo activation of platelets in patients with glomerulonephritis.

The natural history of IgA nephritis in Singapore.

The clinical and histological features of 151 patient with IgA nephritis were analyzed to determine the prognostic features of the disease. The mean duration of follow up examinations was 50 +/- 34 months (range 6 to 168 months). The majority of the patients were young males and showed no signs of IgA nephritis. The disease was detected by routine screening before induction into national service. The plot of the reciprocals of serum creatinine against time in the patients with progressive disease showed that the patients ran two different courses when they developed renal impairment; one was a slow progressive course over an average of 7.7 years before reaching end stage renal failure (ESRF), while the other was a more rapid decline to ESRF within an average of 3.3 years in which severe uncontrolled hypertension seemed to be the major adverse factor. Hypertension was present in 23% of patients. Nine percent had renal impairment at the end of the follow up period while 5% progressed to ESRF. The cumulative renal survival was 91% after 6 years with no further development of renal failure up to 14 years. Unfavorable long term prognostic indices were proteinuria of more than 2 gm, hypertension and presence of crescents on renal biopsy.

Effects of triple therapy on the progression of mesangial proliferative glomerulonephritis.

Fifty-two pairs of patients with idiopathic diffuse mesangial proliferative glomerulonephritis entered a controlled 3-year prospective trial of a combination regimen of cyclophosphamide, dipyridamole and warfarin. In the treatment group proteinuria decreased significantly (p less than 0.01) and renal function remained stable, but in the control group there was no change in proteinuria and creatinine clearance (Ccr) decreased significantly (p less than 0.01). The time patients with renal impairment in the control group and those in the treatment group took to reach end stage renal failure was significantly different (6.1 years versus 8.9 years, p less than 0.02). Among the patients with IgA nephritis, those in the treatment group (n = 27) had stable renal function and a significant decrease in proteinuria (p less than 0.01) but in the control group (n = 21) there was a significant fall in Ccr (p less than 0.01) and rise in serum creatinine (p less than 0.02) with no change in proteinuria. Among 23 pairs of patients in the study who were matched for renal function and degree of glomerulosclerosis, those in the treatment group had stable renal function and decrease in proteinuria (p less than 0.01) whereas those in the control group had decreased Ccr (p less than 0.01) but no change in proteinuria.

Hepatitis C antibodies in patients on peritoneal dialysis: prevalence and risk factors.

Our objective was to determine the prevalence of the antibody to hepatitis C (anti-HCV) in a population of end-stage renal failure patients on continuous peritoneal dialysis (CPD) and study the possible risk factors associated with anti-HCV seropositivity and seroconversion. A cross-sectional study included 155 adult patients enrolled in the CPD program in a single renal unit of a teaching hospital who were screened for anti-HCV by second-generation enzyme immunoassay, which was confirmed by recombinant immunoblot assay. Serum was also assayed for hepatitis B surface antigen (HBsAg). History of renal transplantation, blood transfusions, and exposure to hemodialysis was obtained from medical records. Ten of 155 patients (6.5%) in this study population were anti-HCV positive [anti-HCV(+)] and 11/155 (7.1%) were HBsAg positive; no patient was positive for both. All the anti-HCV(+) patients were on continuous ambulatory peritoneal dialysis (CAPD); no continuous cycling peritoneal dialysis (CCPD) patient was anti-HCV(+). Exposure to hemodialysis was a risk factor for anti-HCV seropositivity, with 7 out of 10 (70%) anti-HCV(+) patients having been on hemodialysis compared to 55/134 (41%) anti-HCV(-) (p < 0.05, Fisher's exact test). No difference was noted between anti-HCV(+) and anti-HCV(-) groups in relation to age, gender, duration on CPD, renal transplantation, or exposure to blood transfusions. Seroconversion occurred in only one patient after a mean observation period of 20 +/- 0.6 months. The prevalence of anti-HCV seropositivity in this population of CPD patients is 6.5%, and HBsAG 7.1%. Exposure to hemodialysis is a significant risk factor for development of anti-HCV seropositivity. Seroconversion rate appears to be low.

The Singapore Renal Registry: an overview.

The Singapore Renal Registry (SRR) is created to collect and analyse information on incidence, prevalence, morbidity and mortality of End Stage Renal Disease (ESRD) in Singapore. Its objectives include the implementation of a consolidated renal disease data system, report on incidence and trends over time of renal disease, analyse aggregate data on effect of various modalities of therapy, identify problems and opportunities for special studies and research. The framework of the Registry encompasses the following areas: incidence, demographics and causes of ESRD, utilization of treatment modalities, institutions providing treatment, morbidity and survival rates of various treatment modalities, the paediatric sector, the private sector, international comparisons and research areas. This overview will present whatever existing data and renal statistics that are currently available on a regional or national basis. The collection of nationwide statistics will provide a database to formulate national averages of individual renal statistics. Statistics can also be collected to provide valuable data for planning and projection for future needs.

Conducting clinical trials in Singapore.

All clinical trials in Singapore will now have to conform to the Medicines (Clinical Trials) Amended Regulations 1998 and the Singapore Good Clinical Practice (GCP) Guidelines 1998. The Medical Clinical Research Committee (MCRC) has been established to oversee the conduct of clinical drug trials in Singapore and together with the legislations in place, these will ensure that clinical trials conducted in Singapore are properly controlled and the well-being of trial subjects are safe guarded. All clinical drug trials require a Clinical Trial Certificate from the MCRC before the trial can proceed. The hospital ethics committee (EC) vets the application for a trial certificate before it is sent to MCRC. The drug company sponsoring the trial has to indemnify the trial investigators and the hospital for negligence arising from the trial. The MCRC, apart from ensuring the safety of trial subjects, has to provide continuing review of the clinical trial and monitors adverse events in the course of the trial. The EC will conduct continuing review of clinical trials. When a non-drug clinical trial is carried out, the EC will ensure that the proposed protocol addresses ethical concerns and meets regulatory requirements for such trials. There is great potential for pharmaceutical Research & Development (R&D) in Singapore. We must develop our skills and infrastructure in clinical trials to enable Singapore to be a regional hub for R&D of drugs in Asia.

Proteinuria: clinical signficance and basis for therapy.

Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure.

Slow continuous ultrafiltration (SCUF)--the safe and efficient treatment for patients with cardiac failure and fluid overload.

Slow Continuous ultrafiltration (SCUF) was first used in 1980 as an alternative mode of fluid removal for patients with oliguric acute renal dysfunction from whatever causes. The advantage of this treatment is that haemodynamic parameters remain stable in the presence of significant removal of fluid. We are describing our experience in 7 patients [age: 57 +/- 9 years; 4 male, 3 female] with cardiac failure and fluid overload who had undergone 8 sessions of SCUF. All of them had renal impairment and were resistant to diuretics. Blood lines were attached to a Kawasumi Renak-E dialyser (Cuprophane membrane) in series using Gambro AK10 dialysis blood pump. The following parameters were monitored: Blood pump (Qb): 175 +/- 26 ml/min, time (T): 393 +/- minutes. Venous pressure averaged a55 +/- 24 mmHg. We achieved ultrafiltration of 2,189 +/- 699 ml/session or 5.5 +/- 1.7 ml/hr. There was no significant change in blood pressure [systolic pre: 143 +/- 14, post: 136 +/- 13 mmHg, not significant; diastolic pre: 87 +/- 10, post: 83 + 10 mmHg, not significant and pulse rate [pre: 87 +/- 9 vs post: 84 +/- 2 per minute, not significant. Heparin dosage averaged 274 +/- 26 IU/hr during the SCUF. We conclude that SCUF is beneficial to diuretic resistant patients with cardiac failure and fluid overload in whom dialysis treatment is not required.