Endothelin-1 in chronic renal failure and hypertension

Investigation into the role of endothelin-1 (ET-1) in renal function has revealed two major direct actions leading to the control of extracellular volume and blood pressure. These are the regulation of renal hemodynamics and glomerular filtration rate and the modulation of sodium and water excretion. In the rat remnant kidney model of chronic renal failure, ET-1 production is increased in blood vessels and renal tissues. These changes are related to an increase in preproET-1 expression and correlate with the rise in blood pressure, the development of cardiovascular hypertrophy, and the degree of renal insufficiency and injury. Selective ETA receptor blockade prevents the progression of hypertension and the vascular and renal damage, supporting a role for ET-1 in chronic renal failure progression. The increase in ET-1 production can be associated with other local mediators, including angiotensin II, transforming growth factor-beta1 and nitric oxide, the local production of which is also altered in chronic renal failure. In human patients with essential hypertension, atherosclerosis, and nephrosclerosis, plasma ET-1 levels are increased compared with patients with uncomplicated essential hypertension. Similarly, plasma ET-1 concentrations are markedly increased in patients with end-stage renal disease undergoing dialysis, and this correlates with blood pressure, suggesting that ET-1 may contribute to hypertension in these patients. The treatment of anemia in patients with renal failure with human recombinant erythropoietin increases blood pressure by accentuating the underlying endothelial dysfunction and the elevated vascular ET-1 production. Overall, these results support a role for ET-1 in hypertension and the end-organ damage associated with chronic renal failure. ETA receptor blockade may then represent a potential target for the management of hypertension and cardiovascular and renal protection.     

Increased protein level of PEPT1 intestinal H+-peptide cotransporter upregulates absorption of glycylsarcosine and ceftibuten in 5/6 nephrectomized rats

In chronic renal failure (CRF), dietary protein is one of the factors that deteriorates residual renal functions. Numerous studies have indicated that the products of protein digestion are mainly absorbed as small peptides. However, how small peptides are absorbed in CRF remains poorly understood. H(+)-coupled peptide transporter (PEPT1/SLC15A1) plays an important role in the absorption of small peptides and peptide-like drugs in the small intestine. Because dietary protein intake is one of the risk factors for renal failure, the alteration of intestinal PEPT1 might have implications in the progression of renal disease as well as the pharmacokinetics of peptide-like drugs. In this study, we examined the alteration of intestinal PEPT1 in 5/6 nephrectomized (5/6 NR) rats, extensively used as a model of chronic renal failure. Absorption of [(14)C]glycylsarcosine and ceftibuten was significantly increased in 5/6 NR rats compared with sham-operated rats, without a change in intestinal protease activity. Western blot analysis indicated that the amount of intestinal PEPT1 protein in 5/6 NR rats was increased mainly at the upper region. On the other hand, the amount of intestinal PEPT1 mRNA was not significantly different from that of sham-operated rats. These findings indicate that the increase in absorption of small peptides and peptide-like drugs, caused by the upregulation of intestinal PEPT1 protein, might contribute to the progression of renal failure as well as the alteration of drug pharmacokinetics.     

Prevalence of advanced renal failure in Northern Ireland.

OBJECTIVE--To determine the prevalence of advanced chronic renal failure in Northern Ireland as part of an assessment by the Renal Association of the level of service provision for treatment of such patients. DESIGN--Prospective notification of patients reaching a defined level of advanced chronic renal failure (serum creatinine concentration greater than or equal to 500 mumol/l or blood urea concentration greater than or equal to 25 mmol/l) within one year and follow up for at least three, and, at most, four years after notification. SETTING--Northern Ireland. PATIENTS--122 Patients with a serum creatinine or blood urea concentration higher than the defined level newly detected from 1 March 1985 to 28 February 1986. MAIN OUTCOME MEASURE--Survival after notification. RESULTS--77 Patients of all ages/million population/year had advanced chronic renal failure compared with 67/million/year between the ages of 5 and 80 found in an earlier study of the same population. 62% Of the patients were older than 50 years. Seventeen (14%) of the patients either required dialysis or died within one month of notification, 51 (42%) survived for at least three months, and 23 (19%) for one year or longer. Three patients, all of whom were attending a renal clinic, survived for periods of 43, 45, and 46 months respectively without renal replacement treatment. CONCLUSIONS--The increased number of new patients disclosed in this survey compared with the earlier survey is mainly owing to an increased number of older patients. Such patients often have disabilities other than renal failure, are less likely to be capable of self treatment, may develop complications more often and require more frequent hospital admissions, and may not be suitable for transplantation and consequently have considerable resource implications for the NHS.     

Asymmetrical (ADMA) and symmetrical dimethylarginine (SDMA) as potential risk factors for cardiovascular and renal outcome in chronic kidney disease – possible candidates for paradoxical epidemiology?

Summary. Background: Asymmetrical dimethylarginine (ADMA) is an inhibitor of nitric-oxide synthase. It has been linked to atherosclerotic risk in the general population as well as in end-stage renal disease patients (ESRD), whereas symmetrical dimethylarginine (SDMA) is thought to be biological inactive. Prospective data concerning the role of both dimethylarginines are rare in patients with chronic kidney disease. Methods: 200 patients with chronic kidney disease (mean age 57.6 ± 13.0 years, 69 female, 131 male); 82 with chronic renal failure (CRF), 81 on maintenance haemodialysis (HD) and 37 renal transplant recipients (RTR) were prospectively followed for 24 months. ADMA and SDMA were measured by HPLC. The relation of plasma levels of ADMA and SDMA together with conventional risk factors for the cardiovascular and renal outcome was investigated with Cox proportional hazards model. Results: Mean serum levels of SDMA were significantly increased in all groups compared to the control group (P ≤ 0.0005), ADMA was increased only in HD and RTR (P ≤ 0.004). Forty-seven cardiovascular events (CVE) occurred during follow-up, 35 patients died, and 39 patients reached ESRD. Multivariate analysis showed diabetes (RR 3.072, P = 0.01), ESRD (RR 11.915, P < 0.0005), elevated CRP levels (RR 3.916, P < 0.0005) and surprisingly a lower ADMA level (RR 0.271, P = 0.008) as independent risk factors for CVE. Serum creatinine (RR 11.378, P = 0.001), haemoglobin (RR 0.710, P = 0.038 for an increment of 1 mmol/l), and SDMA levels (RR 1.633, P = 0.006, per 1 μmol/l increment) were predictors for the progression to ESRD. Conclusions: Data from a heterogeneous group of patients with chronic kidney disease provide evidence that conventional risk factors seem to play a more important role than elevated serum levels of ADMA or SDMA for cardiovascular events. Increasing serum SDMA concentration seems to play an additive role for the renal outcome besides serum creatinine and haemoglobin levels. Whether ADMA might possibly be a candidate for the phenomenon of “paradoxical epidemiology” in chronic kidney disease needs further investigation.     

铜蓝蛋白、鳞状细胞癌相关抗原与慢性肾功能衰竭的关系及对病情进展的预测价值研究

摘要 目的：分析铜蓝蛋白（CER）、鳞状细胞癌相关抗原（SCCA）与慢性肾功能衰竭的关系及对病情进展的预测价值。方法：选择我院自2019年4月至2021年4月接诊的169例慢性肾功能衰竭患者作为研究对象,根据24 h尿白蛋白定量分为微量白蛋白尿组（＜200 mg/24 h,102例）和大量白蛋白尿组（＞200 mg/24 h,67例）。比较两组各项实验室指标及血清CER、SCCA水平,分析CER、SCCA与慢性肾功能衰竭患者肾功能指标的关系。随访12个月,观察病情进展,使用受试者工作特征曲线（ROC）评价血清CER联合SCCA对病情进展的预测效能。结果：大量白蛋白尿组血清肌酐（Scr）、血尿素氮（BUN）水平均明显高于微量白蛋白尿组,肾小球滤过率（GFR）低于微量白蛋白尿组（P＜0.05）;大量白蛋白尿组血清CER、SCCA水平均高于微量白蛋白尿组（P＜0.05）;经Pearson相关性分析,慢性肾功能衰竭患者血清CER、SCCA水平均与Scr、BUN呈正相关,与GFR呈负相关（P＜0.05）;经多因素Logistic回归分析,GFR、CER、SCCA均是慢性肾功能衰竭患者病情进展的独立预测因素（P＜0.05）;经ROC曲线分析,血清CER联合SCCA预测慢性肾功能衰竭患者病情进展的AUC为0.925,明显大于GFR的0.620（P＜0.05）。结论：血清CER、SCCA水平与慢性肾功能衰竭患者肾功能呈负相关,联合预测病情进展效能较好,值得临床予以重视应用。     

Randomised controlled trial of enalapril and beta blockers in non-diabetic chronic renal failure.

OBJECTIVE--To compare the ability of angiotensin converting enzyme inhibitors and beta blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure. DESIGN--Open randomised multicentre trial with three year follow up. SETTING--Outpatient departments of six French hospitals. PATIENTS--100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 mumol/l. 52 randomised to enalapril and 48 to beta blockers (conventional treatment). INTERVENTIONS--Enalapril or beta blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg. RESULTS--17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P < 0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89 x 10(-5)l/mumol/month) than in the enalapril group (-4.17 x 10(-5)l/mumol/month; P < 0.05). No difference in blood pressure was found between groups. CONCLUSION--In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with beta blockers. This effect was probably not mediated through controlling blood pressure.     

Erythropoietin therapy in patients with chronic renal failure.

Symptomatic anemia is a common complication of chronic renal failure. Treatment is now possible with the availability of recombinant human erythropoietin (epoetin alfa). Previous experimental studies have suggested that correcting the anemia of chronic renal failure may be harmful in that renal failure may be accelerated. Although experience with this drug has been primarily restricted to its use in patients with end-stage renal disease, several recent trials have been reported in patients with varying degrees of chronic renal failure. We review these studies with particular reference to the progression of renal failure and the drug''s reported side effects. We conclude that the use of epoetin is beneficial and well tolerated and that there is no compelling evidence for the acceleration of renal failure associated with its use in patients.     

DO RESTLESS LEGS SYNDROME (RLS) AND PERIODIC LIMB MOVEMENTS OF SLEEP (PLMS) PLAY A ROLE IN NOCTURNAL HYPERTENSION AND INCREASED CARDIOVASCULAR RISK OF RENALLY IMPAIRED PATIENTS?

Hypertension can cause or promote renal failure and is related to cardiovascular mortality, the major cause of death in patients with renal impairment. Changes in the circadian BP pattern, particularly the blunting or reversal of the nocturnal decline in BP, are common in chronic renal failure. These changes in turn are among the major determinants of left ventricular hypertrophy. Using a chronobiological approach, it is possible to obtain better insight into the reciprocal relationship between hypertension, renal disease, and increased cardiovascular risk of renal patients. Disruption of the normal circadian rhythm of rest/activity may be hypothesized to underlie the high cardiovascular morbidity and mortality of such patients. Epidemiological studies reveal that hemodialysis patients experience poor subjective sleep quality and insomnia and, in comparison to healthy persons, are more likely to show shorter sleep duration and lower sleep efficiency. Sleep apnea may be present and is usually investigated in these patients; however, the prevalence of restless legs syndrome (RLS), which is high in dialysis patients and which has been associated with increased risk for cardiovascular disease in the general population, could also play a role in the pathogenesis of sleep-time hypertension in renal patients. Careful assessment of sleep quality, in particular, diagnostic screening for RLS and periodic limb movements (PLM) in renal patients, is highly recommended. In renal failure, attention to sleep quality and related perturbations of the sleep/wake cycle may help prevent the occurrence and progression of cardiovascular disease. (Author correspondence: prf@unife.it)     

Selective effect of low protein diets in chronic renal diseases.

It has recently been established that the rate of progression of chronic renal failure in man can be slowed by restricting dietary protein. Consequently, the short term and long term effects of a low protein diet on the course of different chronic nephropathies were studied in an attempt to delineate the factors that determine the response to such a diet. When a low protein diet was given for six months renal function improved significantly in nine patients with chronic tubulointerstitial nephritis (p less than 0.025); the diet had a marginally beneficial effect in 12 patients with chronic glomerulonephritis (p less than 0.05) and no effect in nine with hypertensive nephrosclerosis. The heterogeneous functional response in the patients with chronic glomerulonephritis correlated closely with the effect of the diet on these patients'' proteinuria (r = 0.76, p less than 0.01). In a short term study (four weeks) of 12 patients with chronic renal failure changes in renal plasma flow were proportional to dietary protein intake. Renal vascular resistance fell during a high protein diet and increased when dietary protein was restricted. The changes in renal plasma flow during the low protein diet correlated well with the patients'' long term functional response to the diet (r = 0.76, p less than 0.01). It is concluded that the response to a low protein diet in chronic renal failure is determined, firstly, by the nature of the underlying nephropathy, with maximal benefit being observed in non-glomerular disorders; secondly, by the effect of the diet on the proteinuria in chronic glomerulonephritis; and, thirdly, by the haemodynamic response to the diet, with patients with a reactive renal vascular bed improving with a low protein diet.     

The Clinical Spectrum of Renal Insufficiency During Acute Glomerulonephritis in the Adult

Twenty-seven adults with acute poststreptococcal glomerulonephritis were divided into two groups according to the severity of reduction in renal function: (1) 14 patients with mild depression of renal function, and (2) 13 patients with more severe renal insufficiency. In the first group the outcome was favourable, with complete clinical recovery in 11 patients. Only two patients in the second group have recovered. Five have died of renal failure and in six the chronic stage has developed. The most notable histopathological lesion observed in this group of patients was severe proliferative glomerulonephritis with a large number of epithelial crescents. According to the mode of development and time of onset of renal failure, these 13 patients could be divided into three sub-groups: (1) early renal failure without oliguria (three patients), (2) early renal failure with severe oliguria or anuria (three patients) and (3) delayed renal failure (seven patients).Although there are exceptions, the development of renal insufficiency in an adult patient suffering from acute glomerulonephritis is usually associated with a guarded prognosis.     

Tubular Overexpression of Gremlin Induces Renal Damage Susceptibility in Mice

A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1) specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage progression. This transgenic mouse model could be used as a new tool for enhancing the knowledge of renal disease progression.     

Association of Angiopoietin-2 with Renal Outcome in Chronic Kidney Disease

Background

The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians'' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.

Methods

This study enrolled 621 patients with stages 3–5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m²/y) over follow-up of more than 3 years.

Results

Of all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06–2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13–7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2.

Conclusions

Ang-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.     

Tubulo-interstitial fibrosis: an emerging major health problem

The incidence of chronic kidney disease leading to end-stage renal disease has significantly increased and may reach epidemic proportions over the next decade. Regardless of the initial insult, the progression of most forms of renal disease results in tubulo-interstitial fibrosis. This has been closely correlated to the future appearance of renal failure and has therefore been associated with poor long-term prognosis. New molecules and agents to limit the development of tubulo-interstitial fibrosis and slow down the progression towards end-stage renal disease are needed. In the past twenty years, many efforts have been made to understand the mechanisms of tubulo-intersititial fibrosis with the final goal to develop new therapeutic strategies. In this context, this review will focus on the mechanisms and factors involved in the development and the progression of renal fibrosis and will discuss the new promising therapeutic strategies in animal and humans.     

Loss of collagen-receptor DDR1 delays renal fibrosis in hereditary type IV collagen disease

Alport syndrome is a hereditary type IV collagen disease leading to progressive renal fibrosis, hearing loss and ocular changes. End stage renal failure usually develops during adolescence. COL4A3?/? mice serve as an animal model for progressive renal scarring in Alport syndrome. The present study evaluates the role of Discoidin Domain Receptor 1 (DDR1) in cell–matrix interaction involved in pathogenesis of Alport syndrome including renal inflammation and fibrosis.DDR1/COL4A3 Double-knockouts were compared to COL4A3?/? mice with 50% or 100% expression of DDR1, wildtype controls and to DDR1?/? COL4A3+/+ controls for over 6 years. Double-knockouts lived 47% longer, mice with 50% DDR1 lived 29% longer and showed improved renal function (reduction in proteinuria and blood urea nitrogen) compared to animals with 100% DDR1 expression. Loss of DDR1 reduced proinflammtory, profibrotic cells via signaling of TGFβ, CTGF, NFκB and IL-6 and decreased deposition of extracellular matrix. Immunogold-staining and in-situ hybridisation identified podocytes as major players in DDR1-mediated fibrosis and inflammation within the kidney.In summary, glomerular epithelial cells (podocytes) express DDR1. Loss of DDR1-expression in the kidney delayed renal fibrosis and inflammation in hereditary type IV collagen disease. This supports our hypothesis that podocyte–matrix interaction via collagen receptors plays an important part in progression of renal fibrosis in Alport disease. The blockade of collagen-receptor DDR1 might serve as an important new therapeutic concept in progressive fibrotic and inflammatory diseases in the future.     

Gender and human chronic renal disease

Background: Gender affects the incidence, prevalence, and progression of renal disease. In animal models of the disease, female sex appears to modify the course of progression. Hormonal manipulation by male or female castration also changes the course of renal disease progression, suggesting direct effects of sex hormones in influencing the course of these maladies.Objective: This review examines the pertinent animal and human studies assessing the role of gender, and strives to shed light on the possible physiologic mechanisms underlying the effect of gender, on renal disease progression.Methods: A summary and evaluation of past and recent studies describing the rate of renal disease progression in animal models and humans as it pertains to gender is provided. In addition, studies elucidating the factors involved in the more modest renal progression rate in females are reviewed and conclusions drawn. Relevant English-language publications were identified by searching the PubMed database from January 1990 until November 2007 using the search terms gender, sex, renal disease, and kidney.Results: In polycystic kidney disease, membranous nephropathy, immunoglobulin A nephropathy, and “chronic renal disease of unknown etiology,” men progress at a faster rate to end-stage renal failure than do women. In type 1 diabetes mellitus, there is evidence that males are more likely to manifest signs of renal disease, such as proteinuria. The factors involved in this gender disparity may include diet, kidney and glomerular size, differences in glomerular hemodynamics, and the direct effects of sex hormones. In many, but not all, animal models of renal disease, estrogens slow progression rate. Several studies have recently evaluated the effect of selective estrogen receptor modulators on renal function in humans.Conclusion: Further studies assessing the factors involved in the gender disparity in renal disease progression and the effects of hormonal treatments are warranted.     

Is Fluid Overload More Important than Diabetes in Renal Progression in Late Chronic Kidney Disease?

Fluid overload is one of the major presentations in patients with late stage chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and progression of diabetic nephropathy has been associated with changes in extracellular fluid volume. The aim of the study was to assess the association of fluid overload and diabetes in commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate (eGFR) less than -3 ml/min per 1.73 m²/y) in 472 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. The study population was further classified into four groups according to the median of relative hydration status (△HS =fluid overload/extracellular water) and the presence or absence of diabetes. The median level of relative hydration status was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had commencing dialysis, and 187 (39.6%) subjects presented rapid renal function decline during a median 17.3-month follow-up. Patients with fluid overload had a significantly increased risk for commencing dialysis and renal function decline independent of the presence or absence of diabetes. No significantly increased risk for renal progression was found between diabetes and non-diabetes in late CKD without fluid overload. In conclusion, fluid overload has a higher predictive value of an elevated risk for renal progression than diabetes in late CKD.     

Sex difference in urine concentration across differing ages, sodium intake, and level of kidney disease

Men are known to be at greater risk of urolithiasis and cardiovascular and renal diseases than women. Previous studies suggest that greater urine concentration is associated with acceleration of progression of chronic kidney disease (CKD), increased urinary albumin excretion, and delayed renal sodium excretion. The present review addresses possible sex-related differences in urine volume and osmolality (U(osm)) that could participate in this male risk predominance. Because of the scarcity of information, we reanalyzed 24-h urine data collected previously by different investigators for other purposes. In nine studies concerning healthy subjects (6 studies) or patients with CKD or diabetes mellitus, U(osm) (or another index of urine concentration based on the urine/plasma creatinine concentration ratio) was 21-39% higher (i.e., about a 150 mosm/kgH2O difference) in men than in women. Urine volume was not statistically different. Thus, the larger osmolar load of men (related to their higher food intake) is excreted in a more concentrated urine with no difference in urine volume. This sex difference was not influenced by the level of sodium excretion and was still present in CKD patients. Sex differences in thirst threshold, AVP level, and other regulatory mediators may all contribute to the higher male U(osm). Because of the previously demonstrated adverse effects of vasopressin and/or high urine concentrating activity, the greater tendency of men to concentrate urine could participate in their greater susceptibility to urolithiasis and hypertension and to the faster progression towards end-stage renal failure.     

Chronic renal failure in children.

Seventy-seven children with chronic renal failure were examined at one hospital in the province of Quebec between 1970 and 1975; this represents an incidence of 2.5 per million population per year. The entities responsible for chronic renal failure were urinary tract malformation (in 36%), chronic glomerulonephritis (in 22%), congenital renal parenchymal malformation (in 21%) and hereditary nephropathy (in 13%). The evolution of chronic renal failure in children with either vesicoureteral reflux or a posterior urethral valve seemed to be related more to the initial severity of the disease than to the age at the time of diagnosis. Hence any screening program designed to detect kidney disease in schoolchildren would not prevent chronic renal failure, since at that age renal parenchymal damage seems to be irreversible. The manner in which chronic glomerulonephritis evolved depended on whether the nephrotic syndrome was present and on the type of histologic lesion. Children with congenital renal hypoplasia or dysplasia often presented with seizures due to hypertensive encephalopathy without obvious symptoms or signs of pre-existing renal disease. Among patients with familial nephropathy many of those with cystinosis underwent successful renal transplantation early in life.