Losartan reduces proteinuria and preserves renal function in hypertensive patients with IgA nephropathy

Background. The objectives of this study were to evaluate the effects of the angiotensin II receptor antagonist losartan on blood pressure (BP), proteinuria, and renal function in hypertensive patients with IgA nephropathy. Method. The study subjects comprised 18 patients with biopsy-proven IgA nephropathy with mild hypertension. Patients were classified into three groups (good/relatively good, relatively poor, poor) according to renal histologic findings and treated once a day with losartan 50 mg for 12 months. Changes in BP, proteinuria, renal function, and biochemical parameters were prospectively evaluated before and after the treatment. Results. BP began to fall after 1 month and proteinuria decreased significantly after 9 months of therapy. Glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) did not change throughout the observation period. There was no significant difference between the three different histologic groups in relation to the effects of losartan on BP, proteinuria, and renal function. We found that in patients with a proteinuria reduction rate of more than 50%, RPF increased and FF decreased significantly. Although it has been reported that losartan has a uric acid lowering effect, this study could not confirm such an effect. Conclusions. Losartan lowers blood pressure and decreases proteinuria in hypertensive patients with IgA nephropathy. These effects appear to be independent of renal histologic findings. This study suggests that the antiproteinuric effect of losartan is primarily mediated by changes in glomerular hemodynamics. Received: April 13, 2001/Accepted: July 15, 2002 Correspondence to:H. Ohashi     

Blood pressure, renal function, and proteinuria in children with unilateral renal agenesis

BACKGROUND/AIM: Unilateral renal agenesis (URA) is a model for a reduced nephron number that is believed to be a risk factor for blood pressure (BP) elevation and reduced renal function. The aim of the study was to investigate BP and renal function in children with URA. METHODS: Data on children with URA from two pediatric nephrology centers were firstly retrospectively reviewed (renal ultrasound and scintigraphy, clinical BP, creatinine clearance, urinalysis). Children with normal renal ultrasound and scintigraphy were thereafter investigated using ambulatory BP monitoring. RESULTS: Twenty-nine children with URA were investigated--14 children with an abnormal kidney (mostly scarring) and 15 children with healthy kidneys. Hypertension was diagnosed on the basis of clinical BP in 57% of the children with abnormal kidneys and on the basis of ambulatory BP monitoring in 1 child (7%) with healthy kidneys. The mean ambulatory BP in children with normal kidneys was not significantly different from that in controls. Forty-three percent of the children with abnormal kidneys had a reduced renal function, but none of children with normal kidneys. CONCLUSIONS: Children with abnormalities of a solitary kidney have often hypertension, proteinuria, or a reduced renal function. In contrast, children with healthy solitary kidneys have BP and renal function similar to those of healthy children.     

Blood pressure load,proteinuria and renal function in pre-hypertensive children

It is as yet unclear whether blood pressure load (BPL) can affect renal function in pre-hypertensive children. We have studied 250 children, with a mean age of 9.12 ± 3.28 years, with the aim of assessing if pre-hypertension in children can indeed affect renal function. The study cohort consisted of 146 children with pre-hypertension (group P) and a control group of 104 children with normal blood pressure (group C). All children were tested for orthostatic proteinuria, an exclusion criterion, glomerular filtration rate (GFR), and proteinuria, and ambulatory blood pressure monitoring was performed. Based on the BPL, group P was further subdivided into group P1 (BPL ≤ 40%, low BPL) and group P2 (BPL > 40%, high BPL). We found that GFR was reduced in pre-hypertensive children (90.74 ± 48.69 vs. 110.32 ± 20.30 ml/min per 1.73 m², p < 0.0001) and that proteinuria was increased (145.36 ± 110.91 vs. 66.84 ± 42.94 mg/m² per 24 h; p < 0.0001). However, mean values were still within normal limits. A comparison of the group with high BPL and that with low BPL revealed that the former had relatively reduced GFR (79.15 ± 42.04 vs. 96.78 ± 51.20 ml/min per 1.73 m²; p < 0.006) and increased proteinuria (198.29 ± 142.17 vs. 118.31 ± 80.07 mg/m² per 24 h; p < 0.036). In comparison to the reference values of the normal population, the GFR was reduced and proteinuria was increased in the group with high BPL. Based on our results, pre-hypertension in children with high BPL seems to be associated with reduced GFR and increased proteinuria. A reasonable doubt remains that the patients with higher proteinuria and larger reduction of GFR may harbor an as yet unknown subclinical renal condition responsible for the onset of pre-hypertension. Therefore, children with even mildly elevated BP are at risk of developing renal damage and should change their lifestyle to prevent further increases in BP.     

Effect of fluvastatin and dipyridamole on proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria

AIM: In recent reports, some kinds of HMG-CoA reductase inhibitors were able to decrease proteinuria and to improve renal function. Here we aimed to clarify the effect of fluvastatin (an HMG-CoA reductase inhibitor) on proteinuria and renal function in children with mild IgA nephropathy. PATIENTS AND METHODS: We conducted a prospective controlled study of 30 children who had been recently diagnosed with normocholesterolemic IgA nephropathy following the detection of a minor lesion or of focal mesangial proliferation and moderate proteinuria. The 30 patients were randomly assigned to receive both of 20 mg of fluvastatin and 5 mg/kg of dipyridamole (group 1), or 5 mg/kg of dipyridamole only (group 2) for 1 year. RESULTS: By the end of the trial, urinary protein, hematuria, BUN and serum creatinine levels had significantly decreased in the patients of group 1 as compared to baseline. Serum total cholesterol, triglyceride and LDL cholesterol levels had significantly decreased, while serum total protein and albumin, and creatinine clearance had significantly increased in group 1 as compared to baseline and group 2. The urinary protein level had significantly decreased in the group 2 patients as compared to baseline, but only slightly. CONCLUSIONS: The results of this study suggest that fluvastatin and dipyridamole treatment yields an antiproteinuric effect and leads to the amelioration of renal function in moderately proteinuric patients with mild histological IgA nephropathy.     

Ischemic nephropathy: proteinuria and renal resistance index could suggest if revascularization is recommended

Background: The aim of endovascular therapy in renal artery stenosis (RAS) is to preserve renal function and have a better hypertension control. The purpose of our study was to determine which biochemical and instrumental parameters could predict a better renal outcome in patients with RAS treated with percutaneous transluminal angioplasty and stenting (RPTAS). Methods: We performed an observational study based on 40 patients with RAS who met the following criteria before revascularization: urinary protein excretion of over 250 mg/24 h, normal renal function, and/or mild–moderate renal insufficiency (I, II, and III levels of classification of chronic kidney disease, K-DOQI). Results: Assessment at 12 months after RPTAS showed in 20 patients (Group A) that proteinuria serum creatinine (Scr) and creatinine clearance (CrCl) significantly worsened from the baseline; whereas in 20 patients (Group B) proteinuria remained unchanged and the renal function improved after the procedure. Conclusions: In our study, the decline of renal function after RPTAS is associated with an elevated renal resistance index (RI) in both kidneys (0.83 ± 0.2) and preexisting proteinuria.     

Normal kidney function and elevated natriuresis in young men born with low birth weight

The aim of our study was to characterize renal function and its relationship to blood pressure in healthy young Caucasian men born with a birth weight under 2,500 g (LBW). Urinary protein patterns, N-acetylglucosamine and γ-glutamyltransferase activities, fractional sodium and potassium excretions, glomerular filtration rate, blood pressure, and erythrocyte Na⁺/K⁺-ATPase activities were determined in 65 subjects, of whom 49 were born with LBW. Signs of glomerular or tubular damage were not detected in the LBW population. However, the blood pressure and the renal sodium excretion were inversely correlated to the subjects’ birth weight and were higher in LBW subjects than in controls. In contrast, the erythrocyte Na⁺/K⁺-ATPase activities were lower in LBW subjects. An inverse correlation was detected between the subjects’ Na⁺/K⁺-ATPase activities and the renal sodium excretion or blood pressure. In summary, our results suggest that: (1) in young LBW Caucasian males signs of early glomerular and tubular impairment are not present; (2) the elevated renal sodium excretion may be a result of higher blood pressure; (3) the alteration of Na⁺/K⁺-ATPase activity might play a role either in the elevation of blood pressure and/or in the enhanced natriuresis of LBW subjects. Received: 29 November 1999 / Revised: 20 March 2000 / Accepted: 22 March 2000     

Dominance of blood pressure in natriuresis associated with supraventricular tachycardia.

Supraventricular tachycardia was induced in 10 patients by programmed cardiac stimulation through esophageal lead. Blood pressure, heart rate, renal function, and hormonal factors were measured before, during, and after tachycardia. The patients were divided into two groups, depending on whether antinatriuresis occurred during tachycardia; one group (n = 5) with antinatriuresis during tachycardia associated with a decrease in blood pressure and the other group (n = 5) with neither antinatriuresis nor changes in blood pressure. The urinary sodium excretion tended to increase after tachycardia only in the latter group. On the other hand, urine volume and free water clearance increased during or after tachycardia in both groups. Plasma levels of atrial natriuretic peptide significantly increased and the urinary vasopressin excretion significantly decreased during tachycardia in both groups. During tachycardia, natriuresis due to atrial natriuretic peptide secretion seems to be hampered by hypotension, but polyuria is preserved despite the fall in blood pressure probably related to suppression of vasopressin release.     

Macroscopic hematuria and proteinuria preceding renal IgA deposition in patients with IgA nephropathy

Although the clinical onset of IgA nephropathy is frequently impossible to define, macroscopic hematuria apparently heralds the onset of the disease in some patients. We describe the clinical course and renal histologic findings of four adults with IgA nephropathy who were diagnosed by the characteristic immunohistologic features in a second renal biopsy specimen. IgA was not detected in the initial renal biopsy specimens obtained 9 months to 4 years earlier. The first renal biopsy had been performed to evaluate macroscopic hematuria (recurrent in three patients), accompanied by pathologic proteinuria in two patients. Our observations suggest that the pathognomonic immunohistologic findings of IgA nephropathy may follow the clinical onset and raise questions about the presumed pathogenetic role of IgA in the early stages of this disease.     

Avoidance of polypharmacy and excessive blood pressure control is associated with improved renal function in older patients

Abstract

Background: Elderly patients are particularly susceptible to polypharmacy. The present study evaluated the renal effects of optimizing potentially nephrotoxic medications in an older population. Methods: Retrospective study of patients’ ≥60 years treated between January of 2013 and February of 2015 in a Nephrology Clinic. The renal effect of avoiding polypharmacy was studied. Results: Sixty-one patients were studied. Median age was 81 years (range 60–94). Twenty-five patients (41%) were male. NSAIDs alone were stopped in seven patients (11.4%), a dose reduction in antihypertensives was done in 11 patients (18%), one or more antihypertensives were discontinued in 20 patients (32.7%) and discontinuation and dose reduction of multiple medications was carried out in 23 patients (37.7%). The number of antihypertensives was reduced from a median of 3 (range of 0–8) at baseline to a median of 2 (range 0–7), p?<?0.001 after intervention. After intervention, the glomerular filtration rate (GFR) improved significantly, from a baseline of 32?±?15.5?cc/min/1.73m² to 39.5?±?17?cc/min/1.73m² at t1 (p?<?0.001) and 44.5?±?18.7?cc/min/1.73m² at t2 (p?<?0.001 vs. baseline). In a multivariate model, after adjusting for ACEIs/ARBs discontinuation/dose reduction, NSAIDs use and change in DBP, an increase in SBP at time 1 remained significantly associated with increments in GFR on follow-up (estimate?=?0.20, p?=?0.01). Conclusions: Avoidance of polypharmacy was associated with an improvement in renal function.     

Calcineurin inhibitors and proximal renal tubular injury in renal transplant patients with proteinuria and chronic allograft nephropathy

BACKGROUND: Chronic allograft nephropathy (CAN) is commonly associated with proteinuria. In native nephropathies, proteinuria is linked with proximal renal tubular damage. This study uses regression analysis to link proteinuria with urinary N-acetyl-beta-d-glucosaminidase (NAG) as a marker of tubular injury or hyperfunction in renal transplant patients. METHODS: Proteinuria and urinary NAG were measured and regression analysis applied in 105 transplant patients (42 with CAN). Most were receiving calcineurin inhibitor-based immunosuppression (cyclosporine, n=60; tacrolimus, n=26; and neither drug, n=19). Patients with native nephropathies (n=96) and volunteers (n=21) were also studied. RESULTS: Urinary NAG increased with increasing proteinuria. However, patients taking calcineurin inhibitors had higher urinary NAG at any level of urinary protein than those on alternative therapy, or in native nephropathies. CONCLUSIONS: In groups of transplant patients taking different immunosuppressive regimens, regression analysis of urinary NAG against urinary protein can identify the separate effects of drug-related tubular injury or hyperfunction from that of proteinuria.