Reduced LRP6 expression and increase in the interaction of GSK3ß with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea.

In diabetes mellitus (DM), podocyte apoptosis leads to albuminuria and nephropathy progression. Low-density lipoprotein receptor-related protein 6 (LRP6) is WNT pathway receptor that is involved in podocyte death, adhesion and motility. Glycogen synthase kinase 3 (GSK3) interaction with p53 (GSK3-p53) promotes apoptosis in carcinoma cells. It is unknown if GSK3-p53 contributes to podocyte apoptosis in DM. In experimental DM, green tea (GT) reduces albuminuria by an unknown mechanism. In the present study, we assessed the role of the GSK3ß-p53 in podocyte apoptosis and the effects of GT on these abnormalities. In diabetic spontaneously hypertensive rats (SHRs), GT prevents podocyte's p-LRP6 expression reduction, increased GSK3ß-p53 and high p53 levels. In diabetic SHR rats, GT reduces podocyte apoptosis, foot process effacement and albuminuria. In immortalized mouse podocytes (iMPs), high glucose (HG), silencing RNA (siRNA) or blocking LRP6 (DKK-1) reduced p-LRP6 expression, leading to high GSK3ß-p53, p53 expression, apoptosis and increased albumin influx. GSK3ß blockade by BIO reduced GSK3ß-p53 and podocyte apoptosis. In iMPs under HG, GT reduced apoptosis and the albumin influx by blocking GSK3ß-p53 following the rise in p-LRP6 expression. These effects of GT were prevented by LRP6 siRNA or DKK-1. In conclusion, in DM, WNT inhibition, via LRP6, increases GSK3ß-p53 and podocyte apoptosis. Maneuvers that inactivate GSK3ß-p53, such as GT, may be renoprotective in DM.

Consistência interna e reprodutibilidade da versão em português do critério de diagnóstico na pesquisa para desordens temporomandibulares (RDC/TMD - Eixo II) / Internal consistency and reproducibility of portuguese version of research diagnostic criteria for temporomandibular disorders (RDC/TMD-Axis II)

OBJETIVO: Estudar a confiabilidade, da versão em português, do questionário para o diagnóstico psicológico e psicossocial dos indivíduos com desordens temporomandibulares (RDC/TMD). MÉTODOS: Foram entrevistados 109 indivíduos, de ambos sexos, que demandaram atendimento junto à Clínica de Fisioterapia do Centro Universitário de Araraquara, de janeiro a julho de 2006. Os questionários foram aplicados por um único examinador. Após duas semanas, o mesmo foi reaplicado em 36 indivíduos. Para avaliação da consistência interna do método, utilizou-se o Coeficiente Alfa de Cronbach; para análise da reprodutibilidade intra-examinador, o Coeficiente de Correlação Intraclasse (ro) e a estatística Kappa (kapa), respectivamente às variáveis de natureza quantitativa e qualitativa. RESULTADOS: A consistência interna para as dimensões intensidade da dor crônica e incapacidade; limitação da função mandibular; sintomas físicos não-específicos, incluindo os itens de dor; sintomas físicos não-específicos, excluindo os itens de dor e depressão foi de 0,8479, 0,8971, 0,8673, 0,8080 e 0,9270 respectivamente, atestando ao método excelente validade interna. Obteve-se "excelente" concordância intra-examinador para as questões referentes ao tempo de presença da dor e sua gradação, e "boa" para a questão referente à dor presente. Os menores valores de kapa relacionaram-se aos itens de sintomas físicos e depressão. A percepção de estalos ou rangidos pelos indivíduos apresentou concordância "regular" bem como a questão referente à procura de profissional para tratamento da dor. As demais questões apresentaram reprodutibilidade "boa" e "ótima", sendo que a maioria dessas apresentou nível máximo de concordância. CONCLUSÃO: A versão adaptada para o português mostrou-se confiável para detecção das alterações psicológicas e psicossociais associadas às desordens temporomandibulares.

OBJECTIVE: To study the reliability of the Portuguese version of a questionnaire for psychologically and psychosocially diagnosing individuals with temporomandibular disorders (RDC/TMD). METHOD: Interviews were held with 109 individuals of both sexes who required care at the physical therapy clinic of the Araraquara University Center (UNIARA) from January to July 2006. The questionnaires were applied by a single examiner. Two weeks later, the same questionnaire was reapplied to 36 individuals. To evaluate the internal consistency of the method, Cronbach's alpha coefficient was used. The intra-examiner reproducibility was analyzed using the intraclass correlation coefficient (rho) for quantitative variables and Kappa (kappa) statistics for qualitative variables. RESULTS: The internal consistency for the dimensions of chronic pain intensity, disability, limitations relating to mandibular function, nonspecific physical symptoms with pain items included, and nonspecific physical symptoms with pain items and depression excluded, were 0.8479, 0.8971, 0.8673, 0.8080 and 0.9270 respectively, thus confirming the excellent internal validity of the method. The intra-observer agreement was found to be "excellent" for questions relating to pain duration and intensity and "good" for the question relating to current pain. The lowest kappa values were associated with items relating to physical symptoms and depression. The subjects' perception of clicking and creaking also had "satisfactory" agreement, as did the question on seeking professionals for pain treatment. The remaining questions showed "good" and "very good" reproducibility and most of them presented the maximum agreement. CONCLUSION: The Portuguese adaptation of the questionnaire was shown to be reliable for detecting psychological and psychosocial abnormalities relating to temporomandibular disorders.

Role of caspases on cell death, inflammation, and cell cycle in glycerol-induced acute renal failure.

Caspases are the main executioners of apoptosis as well as interleukin (IL)-1beta and IL-18 conversion to active forms. They are activated after acute kidney injuries. In this study, we evaluated the importance of the caspase family in the pathogenesis and recovery of glycerol-induced acute renal failure in rats (Gly-ARF). Rats were treated with pan-caspase or selective caspase 1 and 3 inhibitors at the moment we injected glycerol. Renal function, renal histology (HE), transferase-mediated deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining for apoptosis, leukocytes infiltration (immunohistochemistry), renal expression of IL-1beta and IL-18 (immunohistochemistry and Western blot), tubular regeneration (5-bromo-2'-deoxyuridine (BrdU) incorporation), and P27(Kip) expression (Western blot) were evaluated at appropriate times. All inhibitors reduced the renal function impairment. Pan-caspase and caspase-3 inhibitors reduced cellular death (necrosis and apoptosis) 24 h after Gly-ARF. All caspases inhibitors reduced macrophages infiltration. The expression of total IL-1beta was enhanced in Gly-ARF, but the active IL-1beta and IL-18 forms were abolished in pan-caspase treated rats. Caspase-1 inhibitor attenuated Gly-ARF but not tubular injury suggesting glomerular hemodynamic improvement. There was striking regenerative response 48 h after Gly-ARF characterized by enhanced BrdU incorporation and reduced expression of p27(Kip). This response was not blunted by caspases inhibition. Our findings demonstrate that caspases participate in important pathogenic mechanisms in Gly-ARF such as inflammation, apoptosis, vasoconstriction, and tubular necrosis. The early inhibition of caspases attenuates these mechanisms and reduces the renal function impairment in Gly-ARF.

Prevention of hypertension attenuates albuminuria and renal expression of fibronectin in diabetic spontaneously hypertensive rats.

BACKGROUND/AIM: The aim of this study was to evaluate the effect of preventing hypertension on renal disease in a model of genetic hypertension and diabetes. METHODS: Four-week-old spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes were randomized for no treatment, or for treatment with captopril, losartan or triple therapy (hydrochlorothiazide, reserpine and hydralazine) for 16 weeks. RESULTS: Increase in systolic blood pressure was equally prevented by captopril (128 +/- 3 mm Hg), losartan (128 +/- 2) and triple therapy (129 +/- 2, p < 0.0001). Albuminuria was similarly reduced by captopril (499 (404-659)), losartan (622 (470-976)) and triple therapy (479 (362-600) microg/24 h (p < 0.0001)). Renal fibronectin expression increased in diabetic SHR (125 +/- 13 densitometric unit) as compared to the controls (51 +/- 9, p < 0.0001), and decreased (p < 0.0001 vs. diabetic SHR) with captopril (32 +/- 8), losartan (27 +/- 4) and triple therapy (35 +/- 6). CONCLUSION: The prevention of hypertension in diabetic SHR by captopril, losartan or triple therapy was equally efficacious in impeding increase of albuminuria and the expression of renal fibronectin. Under these conditions, tight blood pressure control was the main determinant in attenuating nephropathy.

Comparison of the genomes of two Xanthomonas pathogens with differing host specificities.

The genus Xanthomonas is a diverse and economically important group of bacterial phytopathogens, belonging to the gamma-subdivision of the Proteobacteria. Xanthomonas axonopodis pv. citri (Xac) causes citrus canker, which affects most commercial citrus cultivars, resulting in significant losses worldwide. Symptoms include canker lesions, leading to abscission of fruit and leaves and general tree decline. Xanthomonas campestris pv. campestris (Xcc) causes black rot, which affects crucifers such as Brassica and Arabidopsis. Symptoms include marginal leaf chlorosis and darkening of vascular tissue, accompanied by extensive wilting and necrosis. Xanthomonas campestris pv. campestris is grown commercially to produce the exopolysaccharide xanthan gum, which is used as a viscosifying and stabilizing agent in many industries. Here we report and compare the complete genome sequences of Xac and Xcc. Their distinct disease phenotypes and host ranges belie a high degree of similarity at the genomic level. More than 80% of genes are shared, and gene order is conserved along most of their respective chromosomes. We identified several groups of strain-specific genes, and on the basis of these groups we propose mechanisms that may explain the differing host specificities and pathogenic processes.

The presence of genetic hypertension stimulates early renal accumulation of fibronectin in experimental diabetes mellitus.

AIMS/HYPOTHESIS: To investigate the interaction between hypertension and diabetic nephropathy, we studied the renal accumulation of fibronectin in a genetic model of hypertension with streptozotocin-induced diabetes mellitus. METHODS: Spontaneously hypertensive rats (SHR) and their genetically normotensive control Wistar Kyoto rats (WKY) were studied at 4 weeks of age. The rats were killed 20 days after the induction of diabetes mellitus. The renal accumulation of fibronectin was estimated using Western blot analysis as well as immunofluorescence technique and confocal microscopy. RESULTS: Blood glucose concentrations were similar in diabetic SHR rats (27 +/- 3.3 mmol/l) and WKY rats (25.5 +/- 2.7 mmol/l). The systolic blood pressure was higher in both groups of SHR rats than in the control rats. The abundance of renal fibronectin as detected by Western blot analysis was (p < 0.05) higher in the diabetic SHR rats (41.4 +/- 15.0 densitometric U, n = 8) than in the control rats, and no difference was observed between diabetic and control WKY rats (20.8 +/- 6.2, n = 8) and (27.8 +/- 17.2, n = 8). The mean peak intensity of fibronectin signal within the glomerulus as estimated by confocal microscopy was higher (p < 0.05) in the diabetic SHR rats (32.9 +/- 3.5) than in control SHR rats (11.9 +/- 5.7) or diabetic (7.4 +/- 2.2) and control (15.2 +/- 7.9) WKY rats. CONCLUSION/INTERPRETATION: In experimental diabetes the presence of genetic hypertension promotes earlier accumulation of renal fibronectin, a matrix protein implicated in renal glomerulosclerosis.

Characterization of the Brazilian endemic clone of methicillin-resistant Staphylococcus aureus (MRSA) from hospitals throughout Brazil.

The objective of this study was to characterize patterns of the Brazilian endemic clone of methicillin-resistant Staphylococcus aureus (MRSA) from hospitals throughout Brazil. We studied 83 MRSA strains isolated from patients hospitalized in 27 public and private hospitals in 19 cities located in 14 Brazilian states from September, 1995, to June, 1997. The MRSA strains were typed using antibiograms, bacteriophage typing and pulsed field gel electrophoresis (PFGE). The analysis of genomic DNA by PFGE showed that 65 isolates presented the same PFGE pattern. This pattern was present in all of the hospitals studied indicating the presence of an endemic MRSA clone widely disseminated throughout Brazilian hospitals (BEC). All isolates belonging to the BEC proved to be resistant to ciprofloxacin, erythromycin, lincomycin, trimethoprim-sulphamethoxazole, and tetracycline. Variable susceptibility to these drugs was found only in isolates belonging to clones other than the BEC. The results show that, among MRSA, the BEC is common in Brazil. The best method for mapping changes in the frequency of this clone among MRSA is pulsed field gel electrophoresis. Use of molecular mapping is an important tool for monitoring the spread of potentially dangerous microbes.

Erythrocyte sodium-lithium countertransport and proliferative diabetic retinopathy.

PURPOSE: To investigate whether elevated erythrocyte Na+/Li+ countertransport (Na+/Li+ CT) activity is present in patients with proliferative diabetic retinopathy (PDR). METHODS: The rate of Na+/Li+ CT activity assayed in 21 patients with type 1 diabetes mellitus (DM) presenting PDR was compared with 10 patients with nonproliferative retinopathy (NPDR) and with 11 patients with normal fundi. Twelve normal volunteers with no family history of hypertension were used as a control group. The albumin excretion rate was determined by nephelometry, and the glomerular filtration rate was measured by the plasma clearance of eidetic acid labeled with chromium-51. RESULTS: Patients with PDR showed higher diastolic blood pressure levels (mean +/- SD) compared with those with NPDR or normal fundi (95 +/- 13 versus 90 +/- 09 and 82 +/- 19 mm Hg, P = 0.02, respectively). The albumin excretion rate was higher [geometric mean (range)], and the glomerular filtration rate was lower (mean +/- SD) in patients with PDR than in those with NPDR or normal fundi [333 (2 to 5140) versus 32 (5.9 to 2200) and 6 (1.5 to 306) microg/min, P = 0.01, and 63 +/- 33 versus 99 +/- 37 and 93 +/- 43 ml/min, P = 0.02, respectively]. The mean Na+/Li+ CT in patients with PDR was significantly higher than in patients with NPDR or normal fundi and control group (0.46 +/-0.20 versus 0.32 +/- 0.12, 0.32 +/- 11, and 0.21 +/- 0.07 mM/L red blood cells (RBC)/h, respectively, P = 0.0001). In a multiple logistic regression analysis, with PDR as the dependent variable, Na+/Li+ CT (odds ratio [OR]: 4.7, confidence interval [CI]: 1.2-17.6, P = 0.02), diastolic blood pressure (OR, 3.4; CI, 1.3 to 9.6; P = 0.018), and glomerular filtration rate (OR, 5.1; CI, 1.6-17.7; P = 0.007) were the only variables that were maintained in the equation, indicating that they were the main determinants of PDR. CONCLUSIONS: Patients with type 1 DM and proliferative retinopathy have elevated erythrocyte Na+/Li+ CT.

Renal haemodynamic responses to a chicken or beef meal in normal individuals.

BACKGROUND: In normal subjects, protein loading with soybean meal does not produce the same renal haemodynamic effects as those observed with a beef meal. The renal responses of an acute protein load in the form of chicken meal is unknown. METHODS: To examine whether the renal response to a chicken meal differs from that to beef, we studied the renal function of eight normal healthy volunteers before and after a protein load with each of these meals. In a crossover randomized study, we measured the glomerular filtration rate (GFR; inulin clearance), renal plasma flow (RPF; para-aminohippurate clearance) and, plasma amino acid and glucagon levels. We also determined the amino acid content of a sample of chicken and beef. RESULTS: GFR and RPF increased significantly 2 h after both the chicken and beef meals (chicken, 98+/-13 vs 119+/-18 and 476+/-123 vs 570+/-99 ml/min/1.73 m2; beef, 107+/-14 vs 122+/-16 and 501+/-118 vs 560+/-97 ml/min/1.73 m2, for GFR and RPF at basal and 2 h respectively, P<0.05). Renal vascular resistance decreased and the filtration fraction remained unchanged after both protein loads. The changes induced by the protein challenges in the plasma amino acid and glucagon levels were not different between the two protein sources. The amino acid contents of chicken and beef samples were similar. CONCLUSION: In normal subjects, chicken and beef meals induced a similar degree of hyperfiltration.

Band 3 Campinas: a novel splicing mutation in the band 3 gene (AE1) associated with hereditary spherocytosis, hyperactivity of Na+/Li+ countertransport and an abnormal renal bicarbonate handling.

We have studied the molecular defect underlying band 3 deficiency in one family with hereditary spherocytosis using nonradioactive single strand conformation polymorphism of polymerase chain reaction (PCR) amplified genomic DNA of the AE1 gene. By direct sequencing, a single base substitution in the splicing donor site of intron 8 (position + 1G --> T) was identified. The study of the cDNA showed a skipping of exon 8. This exon skipping event is responsible for a frameshift leading to a premature stop codon 13 amino acids downstream. The distal urinary acidification test by furosemide was performed to verify the consequences of the band 3 deficiency in alpha intercalated cortical collecting duct cells (alphaICCDC). We found an increased basal urinary bicarbonate excretion, associated with an increased basal urinary pH and an efficient distal urinary acidification. We also tested the consequences of band 3 deficiency on the Na+/H+ exchanger, by the measurement of Na+/Li+ countertransport activity in red blood cells. The Na+/Li+ countertransport activity was increased threefold to sixfold in the patients compared with the controls. It is possible that band 3 deficiency in the kidney leads to a decrease in the reabsorption of HCO3- in alphaICCDC and anion loss, which might be associated with an increased sodium-lithium countertransport activity.

Mesangial cell abnormalities in spontaneously hypertensive rats before the onset of hypertension.

To identify kidney biosynthetic abnormalities that may precede the onset of hypertension, we studied the expression of fibronectin (FN) and collagen IV (Coll IV) in young SHR (4 weeks of age) whose systolic blood pressure was normal and similar to that of age-matched control WKY rats. In isolated glomeruli the level of FN protein assessed by immunoblotting tended to be lower in the SHR than in the WKY rats. By Northern analysis the FN/actin mRNA ratio was significantly lower in glomeruli from SHR (0.56 +/- 0.47) than in glomeruli from WKY rats (2.0 +/- 0.8). These abnormalities were maintained in vitro since the expression of FN was significantly lower in SHR than in WKY cultured mesangial cells (FN/actin mRNA ratio = 0.84 +/- 0.46 vs. 1.9 +/- 0.7, P = 0.029). No differences in Coll IV mRNA or protein levels were observed in SHR glomeruli and mesangial cells when compared with WKY rats. The levels of aortic FN and Coll IV mRNAs were not different in SHR and WKY rats. In addition, mesangial cells from SHR showed a significantly higher growth rate than those from WKY. The biosynthetic and proliferative abnormalities observed in the SHR mesangial cells appear to reflect genetic characteristics, and could provide novel insights into cellular mechanisms linking the genetics of hypertension with predisposition to glomerular pathology.

Renal functional response to protein loading in type 1 (insulin-dependent) diabetic patients on normal or high salt intake.

Insulin-dependent diabetes mellitus (IDDM) patients may have an increased intrarenal angiotensin II activity. In diabetic patients, captopril increases the renal hemodynamic response to an amino acid infusion. We investigated the effects of two salt diets on arterial pressure and renal response to a protein load in 10 normotensive (blood pressure < 140/90 mm Hg) IDDM patients (aged 30 +/- 3 years) who had diabetes for 7 +/- 4 years and normoalbuminuria levels [albumin excretion rate 4.8 (2.5-19.1) microg/min]. After 1 week of normal (approximately 100 mmol/day; approximately 100 mEq/l) and 1 week of high (approximately 300 mmol/day; approximately 300 mEq/l) salt intake, renal hemodynamic studies were performed at baseline and after a protein load (meat meal) of 100 g/1.73 m2. The mean 24-hour urinary sodium excretion levels were 99 +/- 27 and 293 +/- 80 mmol (mEq) with normal and high salt intake, respectively. No significant changes were seen in plasma sodium and glucose control with the normal and high salt diets, respectively: plasma sodium 135 +/- 3 vs. 137 +/- 1 mmol/l (mEq/l), (p = 0.08) and glycated hemoglobin 9.1 +/- 1.9 vs. 9.4 +/- 2.1% (p = 0.36). The body weight (70.9 +/- 12 vs. 71.8 +/- 13 kg; p = 0.015) was significantly higher with a high salt diet. The mean arterial pressure was similar with both diets (normal vs. high salt diet 91 +/- 9 vs. 89 +/- 6 mm Hg, p = 0.25). The plasma renin concentration [28 +/- 15 vs. 16 +/- 6 microU/ml(168 +/- 90 vs. 96 +/- 36 pmol/l), p = 0.013] and angiotensin II [8.8 +/- 4.4 vs. 6.4 +/- 3.5 pg/ml (0.052 +/- 0.025 vs. 0.038 +/- 0.021 nmol/l), p = 0.016] were significantly lower with the high salt diet. Following protein loading, the glomerular filtration rate increased with both diets: normal salt diet 114 +/- 26 vs. 128 +/- 30 ml/min/1.73 m2(1.9 +/- 0.43 vs. 2.13 +/- 0.50 ml/s/1.73 m2), p = 0.04; high salt diet 118 +/- 23 vs. 127 +/- 29 ml/min/1.73 m2 (1.97 +/- 0.38 vs. 2.12 +/- 0.48 ml/s/1.73 m2), p = 0.13. The change in renal plasma flow was similar to that of the glomerular filtration rate with normal and high salt intake, respectively: 566 +/- 94 vs. 617 +/- 142 ml/min/1.73 m2 (9.44 +/- 1.57 vs. 10.29 +/- 2.37 ml/s/173 m2), p = 0.0017; 572 +/- 125 vs. 600 +/- 110 ml/min/1.73 m2 (9.54 +/- 2.08 vs. 10.00 +/- 1.83 ml/s/1.73 m2), p = 0.057. In this subset of normotensive normoalbuminuric IDDM patients, a high salt intake did not promote an exaggerated renal response to the protein load despite inhibition of the renin-angiotensin system.

Prevalência da nefropatia diabética em pacientes adultos com insuficiência renal crônica terminal / Prevalence of diabetic nephropathy in adult patients with chronic end stage kidney failure

A nefropatia diabética é uma causa freqüente de insuficiência renal crônica terminal (IRTC) entre pacientes admitidos para tratamento dialítico e/ou transplante. OBJETIVO. Avaliar a prevalência a nefropatia diabética (ND) como provável causa da insuficiência renal crônica terminal (IRCT). MÉTODOS. Foram estudados 1.303 [homens (H) = 767 e mulheres (M) = 536] pacientes inscritos para transplante renal com doador cadáver na Disciplina de Nefrologia do HC-UNICAMP, no período de agosto/90 a junho/93 - grupo 1 - e, em 193 (H=112, M=81) indivíduos admitidos para tratamento dialítico no período de um ano (abril/92 a março/93), no município de Campinas. RESULTADOS. A prevalência da ND foi 10,1 por centro no grupo 1 e 17,6 por cento no grupo 2 (x 2 = 7,15; p = 0,007), constituindo a terceira causa de IRCT e precedida pelas glomerulonefrites e hipertensao arterial. No grupo 1, a reduçao no número de pacientes com o aumento do tempo em diálise foi significativamente maior nos pacientes com ND (x 2 = 30,9; p < 0,001). Entre os pacientes com nefropatia diabética, 35 (26 por cento) do grupo 1 e seis (18 por cento) do grupo 2 tinham menos de 35 anos de idade por ocasiao da admissao para o tratamento dialítico e, muito provavelmente, representam pacientes com diabetes melito tipo 1 (insulinodependente). CONCLUSAO. Em nosso meio, a nefropatia diabética é uma causa freqüente de IRCT.

[Prevalence of diabetic nephropathy in adult patients with chronic kidney failure]. / Prevalência da nefropatia diabética em pacientes adultos com insuficiência renal crônica terminal.

UNLABELLED: Diabetic nephropathy is a frequent cause of end-stage renal failure in patients admitted for renal replacement therapy. PURPOSE: To evaluate the prevalence of DN, as the underline disease, in patients with ESRF. METHODS: 1,303 [male (M) = 767 and female (F) = 536] patients with ESRF who were on a waiting list for cadaver kidney transplant at Nephrology Unit-University Hospital (HC-UNICAMP), from August/90 to June/93--group 1--and 193 (M = 112 and F = 81) patients admitted for renal replacement therapy in a year period (April/92 to March/93), in the city of Campinas, State of São Paulo, Brazil, were studied. RESULTS: The prevalence of DN was 10.1% in group 1 and 17.6% in group 2 (x2 = 7.15; p = 0.007), being the third cause of ESRF in both groups, and it was preceded by glomerulonephritis and arterial hypertension. In group 1 the reduction of number of patients with increase in duration of dialysis was significantly greater in patients with diabetic nephropathy (x2 = 30.9; p < 0.001). Among patients with DN 35 (26%) in group 1 and 6 (18%) in group 2 had less than 35 years when they were admitted for renal replacement therapy and are likely to be type 1 (insulin-dependent) diabetic patients. CONCLUSION: In our studied groups DN was a frequent cause of ESRF.