Urinary retinol-binding protein as a prognostic marker in the treatment of nephrotic syndrome.

We studied the urinary levels of retinol-binding protein (urRBP), an index of proximal tubular dysfunction, in patients with nephrotic syndrome before and approximately 2 months after the beginning of steroid therapy as a predictor of response to therapy which included for some patients courses of immunosuppressive drugs. Those patients with minimal-change disease, mesangial proliferative glomerulonephritis, and focal-segmental glomerulosclerosis who had normal pretreatment urRBP levels were responsive to treatment; occasionally, responsive patients had an initially elevated urRBP level which normalized during treatment. Contrariwise, those patients with abnormally high levels of urRBP which did not normalize during treatment did not respond to treatment. The chance of a patient with minimal-change disease, mesangial proliferative glomerulonephritis, or focal-segmental glomerulosclerosis and a pretreatment urRBP level equal to or >1.0 mg/l being resistant to steroid treatment is 30 times that of a patient with a urRBP level <1.0 mg/l and even higher, if we consider the levels obtained during treatment.

Idiopathic focal segmental glomerulosclerosis and HLA antigens.

The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS). HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin) with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2%, P < 0.05). In addition, the three patients of Japanese extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease.

Idiopathic focal segmental glomerulosclerosis and HLA antigens

The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS), HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin) with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2 percent, P<0.05). In addition, the three patients of Japanase extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease.

Effect of the antiglucocorticoid RU-486 on glomerular hemodynamics in remnant nephrons.

Endogenous glucocorticoid (GC) has been proposed to play a role in the adaptive functions of remnant nephron and participates in the progression of renal disease. The effect of GC blockade by RU-486 (20 mg/kg), an anti-GC agent, on the progression of chronic renal failure (CRF) was evaluated in Munich-Wistar rats. CRF was induced by 5/6 nephrectomy. Global renal function, glomerular hemodynamics, proteinuria and renal histopathology studies were performed after 60 days of CRF induction. RU administration in control or CRF groups did not induce significant changes in total renal function, mean arterial or intraglomerular hydraulic pressures, 24-hour proteinuria or sclerosis index. However, RU induced a significant reduction in single-nephron glomerular filtration rate in the superficial nephrons in both groups' control (decreases 20%) and CRF (decreases 57%), without changing total glomerular filtration rate, when compared with vehicle administration. These reductions were due to a decline in glomerular plasma flow rate (QA) and in glomerular ultrafiltration coefficient (Kf). These data suggest that GC played a role in the adaptive hyperfiltration associated with the compensatory mechanism but did not participate in the genesis of proteinuria or glomerulosclerosis in this experimental model.

Nephrotoxicity of acyclovir and ganciclovir in rats: evaluation of glomerular hemodynamics.

Whole-kidney function and glomerular hemodynamics were evaluated after acute (50 mg/kg, iv, in bolus) and short-term chronic (50 mg mg/kg, ip, 5 days) acyclovir (ACV) and short-term chronic ganciclovir (Gan; 30 mg/kg, ip, 5 days) treatment in envolemic Munich-Wistar rats. The evaluation of whole-kidney function of the ACV groups showed a significant reduction in total GFR (0.96 +/- 0.10 to 0.28 +/- 0.02 mL/min in the acute group, P < 0.05, and 1.04 +/- 0.09 to 0.33 +/- 0.04 mL/min in the chronic group, P < 0.05) with a marked increase in total renal vascular resistance (TRVR) (33 +/- 5 to 122 +/- 26 mm Hg.min/mL in the acute group and 28 +/- 3 to 74 +/- 18 mm Hg.min/mL in the chronic group, P < 0.05) and a reduction in RPF (2.29 +/- 0.25 to 0.81 +/- 0.15 mL/min in the acute group and 2.57 +/- 0.36 to 1.30 +/- 0.40 mL/min in the chronic group, P < 0.05). Conversely, urinary flow (V') was unchanged (3.6 +/- 0.4 to 3.6 +/- 0.2 microL/min in the acute group) or elevated (3.7 +/- 0.6 to 6.6 +/- 1.4 microL/min in the chronic group, P < 0.05). The evaluation of glomerular hemodynamics after ACV treatment showed a reduction in single-nephron GFR (SNGFR) (46.4 +/- 5.3 to 26.2 +/- 3.4 nL/min in the acute group and 38.7 +/- 5.7 to 21.1 +/- 5.7 nL/min in the chronic group, P < 0.05), a significant elevation in total arteriolar resistance (RT) (2.90 +/- 0.44 to 4.94 +/- 0.77 x 10(10) dyn.s.cm-5 in the acute group and 3.72 +/- 0.45 to 9.00 +/- 2.40 x 10(10) dyn.s.cm-5 in the chronic group, P < 0.05) and a severe reduction in glomerular plasma flow rate (QA) (152.6 +/- 29.5 to 103.8 +/- 27.8 nL/min in the acute group and 149.1 +/- 29.8 to 68.5 +/- 10.0 nL/min in the chronic group, P < 0.05). However, the glomerular ultrafiltration coefficient, Kf, was changed only in the chronic group (0.1002 +/- 0.0165 to 0.0499 +/- 0.0090 nL/(s.mm Hg), P < 0.05). After Gan treatment, no changes were observed in GFR (1.04 +/- 0.09 to 0.96 +/- 0.08 mL/min, with the maintenance of RPF (2.57 +/- 0.36 to 2.66 +/- 0.34 mL/min) and a nonsignificant reduction in TRVR (28 +/- 3 to 20 +/- 3 mm Hg.min/mL. The short-term Gan treatment also showed a different pattern in glomerular hemodynamics by inducing an elevation in SNGFR (38.7 +/- 5.7 to 50.3 +/- 2.8 nL/min, P < 0.05) with no changes in QA (150 +/- 30 to 135 +/- 22 nL/min) and a mild vasodilation, RT (3.7 +/- 0.5 to 2.7 +/- 0.3 x 10(10) dyn.s.cm-5, P < 0.05) associated with an increment in Kf (0.1002 +/- 0.0165 to 0.2400 +/- 0.0700 nL/(s.mm Hg), P < 0.05). Thus, ACV induced acute renal failure by reducing GFR and SNGFR by an increase in TRVR and RT with a reduction in RPF and QA. Also, after short-term treatment with ACV, a reduction in Kf led to a reduction of SNGFR. On the other hand, Gan treatment did not induce acute renal failure by the adopted techniques.

Nephrotoxicity of low-osmolality contrast media.

To evaluate renal function after the use of a low-osmolality radiological contrast medium (CM), we prospectively analyzed 39 patients submitted to the following examinations: arteriography (n = 32), phlebography (n = 3), computed tomography (n = 3), angioplasty (n = 1), and retrograde pyelography (n = 1). The patients were divided into three groups: group 1, control, formed by renal donors (CT, n = 11 and 11 exams); group 2, hypertensive patients (HYPT, n = 15 and 16 exams); and group 3, patients with diseases of multiple etiologies (MIX, n = 13 patients and 13 exams). Additionally, the patients were divided according to their renal function into: group 4, with a moderate deficit of renal function, creatinine clearance (CrCl) 25 to 60 mL/min (n = 15 patients and 15 exams); and group 5, with a mild deficit of renal function, CrCl > or = 60 mL/min (n = 14 patients and 14 exams). The CM utilized was ioxaglic acid (Hexabrix) the incidence of acute renal failure (ARF) among the patients studied was 12.5% (5/40), and CrCl was the best parameter to monitor the alterations in renal function, which occurred in 35% of the patients, although the changes were mild, reversible, and did not need any therapeutic interventions. The triggering of ARF in these patients may have been due to multiple factors presented at time of CM examination. Thus, it is not possible to identify a single risk factor. However, it is probable that previous important impairment of renal function was the most expressive risk factor.

Late diagnosis of chronic renal failure.

A comparison was made between patients with a late diagnosis of chronic renal failure (1 month or less before starting dialysis, N = 96) and those with an early diagnosis (6 months or more, N = 45) in terms of the following aspects: referral characteristics during the pre-dialysis phase, demographic details and patient biochemistry prior to maintenance dialysis. Information was obtained by surveying consecutive patients with primary renal disease admitted to a university dialysis unit in São Paulo. Fifty-three percent of all patients surveyed had a late diagnosis. These patients had a lower median duration of symptoms (2 vs 6 months, P < 0.01) and were less likely to be referred for dialysis by a nephrologist (9% vs 51%, P < 0.001) than early diagnosis patients. In the early diagnosis group, 7 patients (16%) had follow-up care for less than 6 months and 11 (24%) did not receive any follow-up; 21 patients (47%) did not follow a low-protein diet. At the start of dialysis, patients with a late diagnosis had higher blood pressure and a higher rate of pulmonary infections (19% vs 4%, P = 0.03). Mean concentrations of BUN, serum creatinine and potassium were significantly higher and mean blood hematocrit was lower for the late diagnosis group. After 3 months of dialysis, the mortality rate was higher in the late than in the early diagnosis group (22.9% vs 6.7%, P = 0.02). Late diagnosis of chronic renal failure and lack of adequate follow-up care, prior to the start of dialysis, are common. Interventions to promote early diagnosis of chronic renal failure and to improve compliance with regular nephrological follow-up can be important to reduce the morbidity and the mortality of patients with chronic renal insufficiency.

Late diagnosis of chronic renal failure

A comparison was made between patients with a late diagnosis chronic renal failure (1 month or less before starting dialysis, N = 9 and those with an early diagnosis (6 months or more, N = 45) in terms to of the following aspects: referral characteristics during the pre-dialysis phase, demographic details and patient biochemistry prior to maintenance dialysis. Information was obtained by surveying consecutive patients with primary renal disease admitted to a university dialysis unit in Sao Paulo. Fifty-three percent of all patients surveyed had a late diagnosis. These patients had a lower median duration of symptoms (2 vs 6 months, P<0.01) and were less likely to be referred for dialysis by a nephrologist (9 per cent vs 51 per cent, P<0.001) than early diagnosis patients. In the early diagnosis group, 7 patients (16 per cent) had follow-up care for less than 6 months and 11 (24 per cent) did not receive any follow-up; 21 patients (47 per cent) did not follow a low-protein diet. At the start of dialysis, patients with a late diagnosis had higher blood pressure and a higher rate of pulmonary infections (19 per cent vs 4 per cent, P= 0.03). Mean concentrations of BUN, serum creatinine and potassium were significantly higher and mean blood bematocrit was lower for the late diagnosis group. After 3 months of dialysis, the mortality rate was higher in the late than in the early diagnosis group (22.9 per cent vs 6.7 per cent, = 0.02). Late diagnosis of chronic renal failure and lack of adequate follow-up care, prior to the start of dialysis, are common. Interventions to promote early diagnosis of chronic renal failure and to improve compliance with regular nephrological follow-up can be important to reduce the morbidity and the mortality of patients with chronic renal insufficiency.

Late diagnosis of chronic renal failure and the quality of life during dialysis treatment.

We evaluated the quality of life of 101 hemodialysis patients who had a late < or = 3 months before starting dialysis, N = 47) or early (> or = 6 months, N = 54) diagnosis of chronic renal failure. At the time of the survey patients had been stable on dialysis for at least 3 months and for less than 24 months; median duration of dialysis was 9.1 months. Quality of life was measured by the kidney disease questionnaire (including the intensity and duration of physical symptoms, fatigue, depression, relationship with others and frustration), the health and life satisfaction indices, functional status (Karnofsky scale), and the time trade-off method. Scores for the several indicators of quality of life were closely similar for the late and early diagnosis groups. Health satisfaction compared to one year prior to dialysis was slightly better for the early diagnosis group. For both groups, functional status was a little worse during the first year of dialysis than one year before its start. In the late diagnosis group, elderly patients and diabetics had more impairment in several dimensions assessed. In addition, in this group greater income was significantly correlated with better physical performance (r = 0.52, P < 0.001) and with health satisfaction (r = 0.36, P = 0.027). These findings suggest that after a median duration of 9 months on a dialysis program, patients with a late and early diagnosis of chronic renal failure have a similar performance in terms of quality of life parameters. Age, diabetes and income are associated with the quality of life of patients with a late diagnosis.

Late diagnosis of chronic renal failure and the quality of life during dialysis treatment

We evaluated the quality of life of 101 hemodialysis patients who had a late (( 3 months before starting dialysis, N=47) or early (( 6 months), N= 54) diagnosis of chronic renal failure. At the time of the survey patients had been stable on dialysis for at least 3 months and for less than 24 months; median duration of dialysis was 9.1 months. Quality of life was measured by the kidney disease questionnaire (including the intensity and duration of physical symptoms, fatigue, depression, relationship with others and frustation), the health and life satisfaction indices, functional status (Karnofsky scale), and the time trade-off method. Scores for the several indicators of quality of life were closely similar for the late and early diagnosis groups. Health satisfaction compared to one year prior to dialysis was slighly better for the early diagnosis group. For both groups, functional status was a little worse during the first year of dialysis than one year before its start. In the late diagnosis group, elderly patients and diabetics had more impairment in several dimensions assessed. In addition, in this group greater income was significantly correlated with better physical performance (r = 0.52, P<0.001) and with health satisfaction (r = 0.36, P= 0.027). These findings suggest that after a median duration of 9 months on a dialysis program, patients with a late and early diagnosis of chronic renal failure have a similar performance in terms of quality of life parameters. Age, diabetes and income are associated with the quality of life of pataients with a late diagnosis.

Acceptance for chronic dialysis treatment: insufficient and unequal.

BACKGROUND: Evidence suggests that a number of end-stage renal disease (ESRD) patients die without receiving dialysis. We investigated and compared ESRD patients who died without receiving treatment and those who were accepted for dialysis. METHODS: All patients starting chronic dialysis in 1991 in the city of Sao Paulo and prospectively registered in the Health Secretariat files were studied. From death certificates we obtained data from all patients dying with an underlying cause associated with chronic renal failure. Medical records from a sample of patients who died without receiving dialysis were reviewed. RESULTS: Of 2127 patients, 1582 (74.7%) received dialysis and 545 (25.6%) did not. The best chance of being dialysed occurred in the 20-29 age group. The age groups with the least chance of receiving dialysis were 0-9 years and over 79 years old. The odds ratio (95% Cl) of not receiving dialysis was 12.42 (6.63-23.82) times greater for patients over 60 years old compared to those aged 10-19 years. Patients with renal failure due to congenital diseases, chronic pyelonephritis, unknown cause, and hypertension were less likely to receive dialysis than those with glomerulonephritis or diabetes. CONCLUSIONS: Our results suggest that many ESRD patients die without receiving dialysis. Age and cause of renal disease influence the chance of being accepted for treatment. Restrictions of treatment need to be corrected to guarantee that maintenance dialysis will be accessible to ESRD patients.

Acesso ao tratamento dialítico crônico: deficiente e desigual / Access to chronic dialysis treatment: deficient and unequal

OBJETIVO. Determinar a fraçao de pacientes com insuficiência renal crônica (IRCT) tratada por meio de diálise no Município de Sao Paulo e investigar a influência da idade em relaçao ao acesso a diálise. MATERIAL E MÉTODOS. Foram estudados todos os pacientes que receberam diálise para IRCT durante o ano de 1991, registrados junto à Secretaria de Saúde do Estado. No mesmo ano, foram também coletadas informaçoes dos indivíduos que morreram tendo com causa básica de óbito doença relacionada a insuficiência renal crônica. Estes últimos dados foram obtidos do Serviço Funerário da Prefeitura de Sao Paulo. Cruzando-se os dados destes bancos de dados foi possível descobrir os pacientes que morreram de IRCT sem ter realizado diálise e calcular a fraçao tratada nas diversas faixas etárias. RESULTADOS. De forma global, 25,6 por cento dos pacientes com IRCT nao receberam tratamento. A partir da idade de 40 anos, houve reduçao progressiva e significante (p<0,001) da fraçao de pacientes tratados conforme aumentou a idade. Até os nove anos de idade a percentagem de tratamento também foi reduzida (29 por cento). Indivíduos nas faixas etárias de 60-69 e 70-79 anos apresentaram chance cerca de 5 e 11 vezes maior, respectivamente, de morrer sem receber tratamento dialítico do que aqueles no grupo etário de 20-29 anos. CONCLUSOES. Os autores estimam que pelo menos um quarto dos pacientes com IRCT morreram em Sao Paulo, em 1991, sem ter recebido tratamento dialítico. Idade é um fator importante de discriminaçao para aceitaçao em programas de diálise crônica.

[Access to chronic dialysis treatment: deficient and unequal]. / Acesso ao tratamento dialítico crônico: deficiente e desigual.

OBJECTIVE: To determine the fraction of patients with end-stage renal disease (ESRD) who received dialysis treatment in the city of São Paulo in 1991 and to investigate the influence of age in the access to dialysis. MATERIAL AND METHODS: All patients who received dialysis for ESRD in the city of São Paulo during 1991, and were registered in the Secretary of Health of São Paulo files were included in the study. In the same year, information was also collected on individuals who died having as basic cause of death a disease related to chronic renal failure. These data were obtained from death certificates files. Using simultaneously information from both data bases it was possible to ascertain the patients who died without receiving dialysis and to calculate the treated fraction in several age groups. RESULTS: Overall 25.6% of ESRD patients did not receive treatment. There was a progressive reduction in the fraction of patients treated for those older than 40 years. In children less or equal to 9 years of age the percentage of treatment was also reduced (29%). Individuals in the age groups 60-69 and 70-79 years had a chance about 5 and 11 times greater, respectively, of dying without receiving dialysis than those in the 20-29 years group. CONCLUSIONS: We estimate that at least one fourth of the ESRD patients died in São Paulo in 1991 without receiving dialysis treatment. Age is a major factor of discrimination for acceptance in chronic dialysis programs.

Fructose-1,6-diphosphate: potential protection in cyclosporine-induced renal impairment.

There is evidence that fructose-1,6-diphosphate (FDP) provides protection from hepatic and cardiac toxic-induced damage and ischemic renal insult. To determine if FDP also protects against cyclosporine (CsA)-induced nephrotoxicity, two groups of adult male Wistar rats were studied for whole kidney clearance rates. After two initial control periods, group 1 received only CsA (CsA, n = 8). Group 2 received FDP 350 mg/kg, followed by CsA 50 mg/kg (FDP-CsA, n = 6). In both groups, after a 30-min equilibration period, two additional clearance rates were measured (Post 1 and Post 2). A significant reduction in clearance rates was observed after drug infusion in both groups (approximately 58 and 64% in CsA and FDP-CsA groups, respectively, p < 0.05) with a recovery to control values in the Post 2 period in the FDP-CsA group. These data suggest a protective effect of FDP on CsA-induced renal impairment.

Sensitivity to calcium intake in calcium stone forming patients.

The absorptive or renal origin of hypercalciuria can be discriminated using an acute oral calcium load test (ACLT). Of 86 patients with calcium oxalate kidney stones, 28 (23%) were found to be hypercalciuric (HCa) and 58 (67%) normocalciuric (NCa) on their customary free diet, containing 542 +/- 29 mg/day (mean +/- SE) of calcium. Since the apparently normal 24-hour calcium excretion of many calcium stone formers (CSF) may be due to a combination of high calcium absorption with moderately low calcium intake, all patients were investigated by ACLT. Of 28 HCa patients, 13 (46%) were classified as absorptive (AH) and 15 (54%) as renal hypercalciuria (RH). Of the 58 NCa patients, 38 (65%) presented features of intestinal hyperabsorption and were therefore designated as AH-like, and 20 (35%) as RH-like. To further elucidate the role of dietary calcium in these CSF, a chronic calcium load test (CCLT), consisting of 1 g/day of oral Ca for 7 days, was designed. A positive response to the CCLT was considered to occur when urinary calcium (uCa) was > or = 4 mg/ kg/24 h on the 7th day. Among NCa patients, 29% of AH-like subjects responded to the CCLT and 71% did not; 50% of RH-like subjects also responded and 50% did not. In HCa patients, 85% of AH and 67% of RH subjects maintained uCa > or = 4 mg/kg/24 h after the CCLT and 15% of AH and 23% of RH subjects did not. However, a significant additional increase in mean uCa was not observed among HCa patients. All patients were submitted to a second evaluation of fasting calciuria (Ca/Cr). A modification of this parameter was noticed in 89% of RH-like and 78% of RH patients. In conclusion, these data suggest the presence of subpopulations of patients sensitive or not to calcium intake, regardless of whether the acute response to a calcium overload test suggested AH or RH. The CCLT disclosed dietary hypercalciuria in 21/58 (36%) of previously NCa patients. In these NCa patients, the ACLT may be replaced by the CCLT. The distinction between AH and RH initially evidenced by the ACLT was not further confirmed. These data suggest that either fasting Ca/Cr is not adequate for subclassification of HCa or that AH and RH represent a different spectrum of the same disease, and that a primary resorptive component should also be considered.

Environmental transmission of hepatitis B and hepatitis C viruses within the hemodialysis unit.

The hepatitis B virus (HBV) can be transmitted in the dialysis setting through blood transfusions and environmental surfaces. Transfusion related hepatitis C virus (HCV) infection is very well known, but only recently the environmental transmission of this virus was postulated. In order to study the prevalence, mechanisms of transmission, and the ALT patterns of HBV and HCV infections in hemodialysis and CAPD patients before the implementation of HBV vaccination and HCV screening in the blood bank, we conducted a study from January 1987 to January 1990. Sera from 185 hemodialysis and 124 CAPD patients were stored in this period and later analyzed for HBsAg, anti-HBc, anti-HBs, and anti-HCV (second generation ELISA). The prevalence of any HBV marker was 55.7% (103/185) for hemodialysis patients and 31.5% (39/124) for CAPD patients (hemodialysis vs. CAPD, p < 0.001). The prevalence of positive anti-HCV was 35.1% (65/185) for hemodialysis and 33.9% (42/124) for CAPD patients (not significant). There was a significant association between HBV markers positivity and anti-HCV positivity. The multivariate analysis of risk factors revealed an association of the positivity of each virus with the duration of renal replacement therapy (RRT), number of previous blood transfusions, and past history of hemodialysis treatment. Thus, besides the transfusion-related transmission, hemodialysis environmental transmission may also occur for both viruses. The findings of a high prevalence of both viruses and evidence for environmental transmission in the dialysis setting are of major importance for the planning of future preventive measures.

Hemodialysis versus continuous ambulatory peritoneal dialysis: effects on the heart.

In this study we compared the influence of 2 different modalities of treatment, CAPD and hemodialysis, on the prevalence and severity of left ventricular hypertrophy and cardiac arrhythmias of chronic renal failure patients. We compared 27 patients on the CAPD program with 27 patients on the chronic hemodialysis matched for sex, age, and duration of dialysis treatment. The prevalence of hypertension was significantly lower in CAPD than in hemodialysis patient (41% vs. 81%, p = 0.0023). Blood pressure levels were also lower in CAPD than in hemodialysis patients (systolic pressure 124.9 +/- 4.7 vs. 154.8 +/- 4.6 mm Hg, p < 0.0001; diastolic pressure 77.5 +/- 2.9 vs. 93.3 +/- 2.8 mm Hg, p = 0.0001). Left ventricular hypertrophy (LVH) was present in 52% of CAPD and in 93% of hemodialysis patients (p = 0.0008). Severe cardiac arrhythmias (Lown 3-4) occurred in only 4% of CAPD and in 33% of the hemodialysis group (p = 0.0149). The lower frequency of LVH in CAPD might explain the lower incidence of severe arrhythmias.