Incidence of microalbuminuria in children with pyelonephritic scarring

There is experimental evidence that loss of renal parenchyma results in hyperfiltration in the remnant glomeruli followed by development of glomerulosclerosis. Microalbuminuria, i.e., a urinary albumin excretion rate of 20 – 200 μg/min, is considered to be an early predictor of diabetic glomerulosclerosis. Hypothetically, increased urinary albumin excretion in patients with pyelonephritic scarring may also indicate glomerulosclerosis, with risk for future deterioration of renal function. This study was performed to determine the incidence of increased albumin excretion in children with mild to moderate pyelonephritic scarring, and to relate the information to glomerular filtration rate (GFR; clearance of inulin) and effective renal plasma flow (clearance of para-aminohippuric acid), as well as to the degree of scarring. The functional investigations were performed under water diuresis. Fifty-seven children, aged 1.7 – 17.9 years, with pyelonephritic renal scarring were included in the study. Nine young healthy adults were used as controls. The GFR was significantly lower in the children with pyelonephritic scarring than in the controls (median 93 ml/min per 1.73 m², range 48 – 133 vs. 111 ml/min per 1.73 m², range 89 – 121, P<0.05), and the urine albumin excretion was significantly higher (median 20 μg/min per 100 ml GFR, range 0.8 – 170 vs. 9.2 μg/min per 100 ml GFR, range 3.3 – 21, P<0.05). An inverse correlation was found between urine albumin excretion and GFR. Increased urine albumin excretion was found in 70% of the children with a GFR below 90 ml/min per 1.73 m² compared with 41% of the children with a GFR above this level. Increased urine albumin excretion (>20 μg/min per 100 ml GFR) was found in 51% of the children with pyelonephritic scarring, while only 14% had increased age-adjusted serum creatinine concentrations. The high incidence of microalbuminuria in children with pyelonephritic scarring indicates long-term follow-up until the ultimate outcome has been better defined. Received January 17, 1995; received in revised form and accepted April 2, 1996     

Urinary protein excretion and renal function in children with IgA nephropathy

Renal haemodynamics and the pattern of urinary protein excretion were studied in 38 children (21 boys, 17 girls) with biopsy-proven IgA nephropathy (IgAN), 0.4–16.8 (median 5.3) years after onset of the disease. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were evaluated by clearances of inulin and para-aminohippuric acid. Serum and urinary albumin, IgG and beta₂-microglobulin (2) were determined and the excretion rates, clearances, and fractional clearances were calculated. The patients were grouped according to the type and the amount of proteinuria. Mean GFR and ERPF were significantly decreased (107±3 and 580±17 ml/min per 1.73 m², respectively) versus controls (119±2 and 627±14 ml/min per 1.73 m², respectively). Grouped according to albumin excretion rates, non-albuminuric patients had normal GFR, while mean GFR was reduced in patients with micro-albuminuria (106±3 ml/min per 1.73 m²) and albuminuric patients (92±7 ml/min per 1.73 m²). IgG excretion increased with increasing albuminuria, but the selectivity index was lower in albuminuric patients than in patients with micro-albuminuria. Albuminuric patients had also higher blood pressure than those with micro-albuminuria. 2 excretion did not discriminate between patients with impaired renal function. The results suggest that childhood IgAN is not a benign kidney disease. After a median duration of 5 years of the disease a number of children had impaired renal function. Mean GFR was reduced most in the albuminuric patients but was also decreased in micro-albuminuric patients, indicating that micro-albuminuria may be a predictor of more severe disease.     

Short-term effect of angiotensin-converting enzyme inhibitor enalapril in incipient diabetic nephropathy

The short-term effect (2 weeks) of angiotensin-converting enzyme inhibitor (enalapril) on renal hemodynamics and urinary albumin excretion was investigated in eleven normotensive patients with incipient diabetic nephropathy (IDN). Six patients had had elevated baseline glomerular filtration rate (GFR) and each responded to enalapril with a decline in the GFR, from a mean of 160.7 to 134 ml/min/1.73 m2, (p less than 0.05). Their respective filtration fraction values also decreased from a mean of 27.8 to 23.8% (p less than 0.01). Such renal hemodynamic change was accompanied by a decrease in urinary albumin excretion (33 to 19 micrograms/min, p less than 0.05). The remaining 5 patients had displayed normal baseline GFR (mean, 109.6 ml/min/1.73 m2), responded to enalapril with minimal change in the GFR (115.2 ml/min/1.73 m2) and showed no significant improvement in their microalbuminuria. It is concluded that enalapril is effective in lowering glomerular filtration pressure and ameliorating microalbuminuria in the normotensive patient with IDN only when the baseline GFR is elevated.     

Relationship between urinary albumin excretion and glomerular filtration rate in normotensive, nonproteinuric patients with type 2 diabetes mellitus

BACKGROUND/AIM: In patients with type 2 diabetes mellitus, the relationship between glomerular filtration rate (GFR) and urinary albumin excretion remains an unresolved issue. In order to investigate the early renal function abnormalities, GFR and urinary albumin excretion were assessed, and their relationship was examined in normotensive patients with type 2 diabetes mellitus. METHODS: In a cross-sectional study of 85 nonhypertensive Japanese patients with type 2 diabetes mellitus not showing overt proteinuria, the GFR was measured using (99m)Tc-diethylenetriamine pentaacetate renography. Fifty-one diabetic patients lacked microalbuminuria (albumin excretion <30 mg/day), while 34 patients showed microalbuminuria (between 30 and 300 mg/day). Fifteen healthy subjects served as controls. RESULTS: The three groups were well matched with regard to gender, age, and body mass index. The GFR in microalbuminuric patients (134 +/- 23 ml/min/1.48 m(2)) was significantly higher than in patients without microalbuminuria (108 +/- 21 ml/min/1.48 m(2)) and in controls (109 +/- 18 ml/min/1.48 m(2); p < 0.0001). In type 2 diabetic patients, the GFR positively correlated with the logarithmically transformed urinary albumin excretion. Multiple regression analysis showed that the urinary albumin excretion was significantly and independently affected by GFR (beta = 0.548), duration of diabetes (beta = 0.297), and systolic blood pressure (beta = 0.232; R(2) = 0.409; p < 0.0001). CONCLUSION: It is suggested that one of the mechanisms underlying increased urinary albumin excretion in early nephropathy in normotensive type 2 diabetes is glomerular hyperfiltration.     

Decreasing glomerular filtration rate - an indicator of more advanced diabetic glomerulopathy in the early course of microalbuminuria in IDDM adolescents?

Background. Overt diabetic nephropathy is accompanied by a progressive decline in glomerular filtration rate (GFR). In this study we have investigated if a reduction of GFR already during the transition from normo- to microalbuminuria is associated with glomerular structural changes. Methods. Seventeen adolescents (11 girls/6 boys) with 10.5 (3.4) (mean, SD) years of IDDM were studied. GFR was previously measured in the normoalbuminuric stage 2-5 years prior to the renal biopsy, and measured again at the time for the biopsy, after in mean 1.8 years of microalbuminuria (15-200 &mgr;g/min). HbAlc and albumin excretion rate were measured 3 or 4 times yearly and blood pressure 1-4 times yearly between the GFR examinations. The associations between the yearly rate of fall in GFR and basement membrane (BM) thickness, mesangial and matrix volume fractions, matrix star volume, mean capillary diameter (CAPD), area of filtration surface (peripheral BM) per glomerulus, total capillary length per glomerulus, the ratio of peripheral BM to capillary surface, glomerular volume, and interstitial volume fraction were analysed. Results. BM thickness and matrix star volume were increased in patients with, as compared to those without, a decline in GFR⩾6 ml/min per year (P<0.005 respectively). Patients with previous glomerular hyperfiltration (⩾135 ml/min per 1.73 m²) showed the steepest decline in GFR; 11 ml/min per year versus -0.8 ml/min per year in previously normofiltering patients, P<0.001. The rate of fall in GFR was positively correlated to BM thickness (P<0.001), interstitial volume fraction (P=0.02) and CAPD (P=0.04), mean HbAlc (P=0.01), but not to the change in HbAlc between GFR examinations. Conclusion. A decreasing glomerular filtration rate in the early stage of microalbuminuria may be due to more advanced diabetic glomerulopathy than in IDDM patients with stable GFR.     

Renal hemodynamic changes and renal functional reserve in children with type I diabetes mellitus

Increased glomerular filtration rate (GFR) has been implicated in the development of diabetic nephropathy. Large normal interindividual variations of GFR hamper the diagnosis of renal hemodynamic alterations. We examined renal functional reserve (RFR) in children with type 1 diabetes mellitus to assess whether hyperfiltration occurs. The renal hemodynamic response following dopamine infusion was examined in 51 normoalbuminuric diabetic children (7.7 ± 3.6 years) with a mean duration of diabetes of 6.2 years and compared them with 34 controls. Mean baseline GFR in diabetic children did not differ from the control population (130.7 ± 22.9 vs. 124.8 ± 25 ml/min per 1.73 m²), whereas renal plasma flow was significantly lower (463.7 ± 103.9 vs. 587.2 ± 105 ml/min per 1.73 m², p < 0.001), and filtration fraction was increased (29 ± 8 vs. 21 ± 2%, p < 0.001), compared with controls. The mean RFR was lower (p < 0.001) than in control subjects (−0.77 ± 23 vs. 21 ± 8 ml/min per 1.73 m²). This study documents an increased filtration fraction and reduced or absent RFR in children with type 1 diabetes mellitus in the stage before apparent nephropathy. GFR values were within normal range. Although the reduced RFR and increased filtration fraction indicate the presence of hemodynamic changes, their relevance to the development of hyperfiltration and subsequent diabetic nephropathy remains unknown.     

Urinary protein excretion and renal function in young people with diabetes mellitus.

To detect early renal involvement in young diabetic patients (IDDM), urinary protein excretion and renal function were examined in 110 patients aged 5.9-25.0 years. Clearances of inulin and PAH were determined as well as albumin (Alb), IgG, N-acetyl-beta-D-glucosaminidase (NAG) and creatinine (Cr) excretion rates (UV). The patients were grouped according to IDDM duration (2- less than 5, 5-10 and greater than 10 years) and albumin excretion rate (non-albuminuria less than 20, microalbuminuria 20-200, and albuminuria greater than 200 micrograms/min per 1.73 m2). Four patients had overt albuminuria, 17 microalbuminuria (equally distributed among the duration groups). Grouped according to albumin excretion rate, the mean GFR was increased in those without albuminuria but 'normalized' in patients with microalbuminuria/albuminuria. Grouped according to albumin excretion rate and the duration of the disease, the non-albuminuric patients with IDDM for greater than 10 years had a lower GFR than those with a shorter duration of IDDM. The patients with microalbuminuria/albuminuria and IDDM for less than 5 years had a reduced GFR. Patients with increased NAG excretion rate had lower Na excretion rate, lower fractional Na excretion and greater creatinine excretion than those with normal NAG excretion. Albumin excretion correlated with IgG excretion, but also with NAG excretion. Our results suggest that early albuminuria in IDDM is of both glomerular and tubular origin. The hyperfiltration declines with increasing albumin excretion but also with the duration of the disease.     

Glomerular function and microalbuminuria in children with insulin-dependent diabetes

Renal function has been evaluated in 45 diabetic children (age 12.5±4 years) with a mean diabetes duration of 4.9±3.5 years. Glomerular filtration rate (GFR; inulin and creatinine clearances), renal plasma flow (RPF; PAH clearance), resting urinary albumin excretion (UAE) were measured and compared with indexes of metabolic control: Hb A₁C and blood glucose values (mean, post-prandial and maximal excursion) on the same day. GFR (inulin clearance) and RPF were significantly increased in the diabetic group (171±31 and 778±172 ml/min per 1.73 m²) compared with controls (124±18 and 631±128 ml/min per 1.73 m²). Both parameters were strongly correlated (r=0.73;P<0.001). Creatinine clearance was not correlated to inulin clearance. Hyperfiltration (inulin clearance above 160 ml/min per 1.73 m²) was noted in 61% of the patients and was independent of diabetes duration. Five diabetic children had a UAE level above 15 g/min. No relationship could be established between UAE and any of the metabolic indexes; GFR was weakly correlated to HbA₁C (r=0.35;P<0.05), to mean (r=0.35;P<0.05) and post-prandial blood glucose (r=0.37;P<0.05). In contrast, there was a strong correlation between GFR and the maximal blood excursion (r=0.62;P<0.001). The study shows that renal abnormalities can be detected with a high frequency in diabetic subjects characterized by both an early onset and a short duration of diabetes and suggests the need for a more systematic evaluation of renal parameters in this population.     

Renal function and kidney size in glycogen storage disease type I

Renal failure has been reported recently as a late complication of glycogen storage disease type I (GSD I). We studied the renal function of 23 patients, mean age 10.9 years (range 2.2–21.6 years). The mean glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 188±50 and 927±292 ml/min per 1.73 m², respectively (normal values for adult controls 90–145 and 327–697, respectively). Hyperfiltration (GFR >145 ml/min per 1.73 m²) was found in 19 of 23 patients. There was no difference in GFR and ERPF between age groups 2–10 and 11–22 years. After a mean follow-up of 2.5 years (range 1–7.5 years) GFR and ERPF did not significantly change. At follow-up 3 patients (all older than 15 years) developed persistent glomerular proteinuria (0.1, 0.5 and 0.9 g/day). Besides a slight increase in fractional excretion of ₂-microglobulin (FE-₂m) in 6 patients, proximal tubular function tests (FE-₂m, tubular reabsorption of phosphate and glucosuria) were normal. In patients with increased kidney length related to body height, GFR and ERPF were significantly higher than in patients with normal kidney length. We conclude that GSD I is characterised by hyperfiltration and hyperperfusion. The relative increment in kidney length is related to the degree of hyperfiltration.     

Renal function during and after childhood acute poststreptococcal glomerulonephritis

It is still debatable whether acute poststreptococcal glomerulonephritis (APSGN) can lead to permanent renal impairment. The clinical, immunological, and histological findings during the acute disease have been described thoroughly, however, the hemodynamic events are still poorly understood. In this retrospective study, the inulin and p-aminohippurate clearances were measured to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) within a month of onset of the disease (acute stage) in 26 children, and 2–12 months after onset (follow-up) in 22 children with APSGN. During the acute stage, the mean GFR was 77±23 (SD) ml/min per 1.73 m², the mean ERPF 537±138 ml/min per 1.73 m², and the filtration fraction (FF) 14%±3%, compared with values for controls of 115±11 ml/min per 1.73 m², 607±72 ml/min per 1.73 m², and 19%±2%, respectively (n=42). At follow-up, GFR was 114±15 ml/min per 1.73 m², ERPF 600±68 ml/min per 1.73 m², and FF 19%±3%. Thus, during the disease both GFR and ERPF fell below values for controls, but later were restored. The GFR, however, was more reduced than the ERPF, as indicated by the reduced FF. This might reflect a relative hyperperfusion of individual nephrons, which might start processes later deleterious to the nephrons. This finding, however, needs to be further investigated and we have therefore started a long-term follow-up of these patients. Received: 24 June 1998 / Revised: 4 December 1998 / Accepted: 7 December 1998     

Glomerular filtration rate in early diabetes: ongoing discussions of causes and mechanisms

Glomerular hyperfiltration (>140 ml/min per 1.73 m2 body surface area) is found in early diabetes and is associated with a poor prognosis with respect to the development of diabetic kidney disease. This review addresses recent investigations and discussions of the following hypotheses behind diabetic hyperfiltration: Increased proximal tubular volume reabsorption results in a pressure drop in Bowman's capsule which increases glomerular filtration rate (GFR). Proximal tubular hyperreabsorption induces an increase in GFR mediated by tubuloglomerular feedback. Dietary NaCl restriction results in a paradoxically increased GFR and increased urine volume in diabetic animals.     

Validation of the Center for Medicare and Medicaid Services algorithm for eligibility for dialysis

The Center for Medicaid and Medicare Services (CMS) has recently revised their end-stage renal disease (ESRD) Medical Evidence Report, Medicare Entitlement, and Patient Registration CMS 2728 Form. The modified algorithm calls for the use of formulae to estimate glomerular filtration rate (GFR). The new criterion is defined as estimated GFR of less than 20 ml/min per 1.73 m². GFR is either estimated by Schwartz formula (C_SCH) in children or Modification of Diet in Renal Disease formula (C_MDRD) in adults. The purpose of this communication is to test the validity of the new CMS GFR algorithm in detecting children who need renal replacement therapy. We evaluated two cohorts of children. Group I included single-center data from 626 ¹²⁵I-iothalamate clearance studies (C_IO) that were compared with the simultaneous estimation of GFR by C_SCH. Group II included data on 659 children from the patient incidence registry obtained from the ESRD Network of Texas between February 1996 and October 2003. In group I there were 76 children (76 C_IO) with C_SCH less than 20 ml/min per 1.73 m² of whom 50 (67%) had C_IO less than 15 ml/min per 1.73 m². Of children with C_IO less than 15 ml/min per 1.73 m², 62% had a C_SCH less than 20 ml/min per 1.73 m². The ability of C_SCH greater than 20 ml/min per 1.73m² to predict C_IO greater than 15 ml/min per 1.73 m² (negative predictive value) is 0.95. The number of children who were started on dialysis in Texas within the study period was 659 (group II). The mean C_SCH±SD was 10.8±7.7 ml/min per 1.73 m². Of the patients who were initiated on dialysis, 94% had C_SCH less than 20 ml/min per 1.73 m². The results were sustained when race, gender, age range, and type of diagnosis were considered. The new CMS algorithm provides a good negative predictive estimate of GFR less than 15 ml/min per 1.73 m². Disclaimer The analyses upon which this publication is based were performed under contract number 500–03-NW14 entitled End-Stage Renal Disease Networks Organization for the State Texas, sponsored by the Centers for Medicare and Medicaid Services, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors assume full responsibility for the accuracy and completeness of the ideas presented. This article is a direct result of the Health Care Quality Improvement Program initiated by the Centers for Medicare and Medicaid Services, which has encouraged identification of quality improvement projects derived from analysis of patterns of care, and therefore required no special funding on the part of this contractor. Ideas and contributions to the author concerning experience in engaging with issues presented are welcomed.     

Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction, and microalbuminuria of incipient diabetic nephropathy in patients

Microalbuminuria, an early feature of diabetic nephropathy, indicates intrarenal endothelial damage. In type 2 diabetes, microalbuminuria is strongly related to insulin resistance. We therefore investigated whether rosiglitazone, an insulin-sensitizing drug that is known to improve endothelial dysfunction, was able to improve intrarenal endothelial dysfunction and microalbuminuria. Nineteen type 2 diabetic patients participated in this double-blind cross-over trial. Nine patients with newly diagnosed disease without microalbuminuria were randomized to a treatment with rosiglitazone or nateglinide, each for 12 weeks. Ten patients with microalbuminuria were randomized to rosiglitazone or placebo, each for 12 weeks in addition to their previous antidiabetic medication. After each treatment, glomerular filtration rate (GFR), renal plasma flow, and filtration fraction were measured before and after blockade of nitric oxide (NO) by intravenous administration of N-monomethyl-L-arginine-acetate (L-NMMA). Ten healthy subjects served as control subjects. Type 2 diabetic patients at baseline showed glomerular hyperfiltration compared with healthy control subjects. Rosiglitazone reduced elevated GFR and filtration fraction toward control primarily in patients with microalbuminuria (GFR: 133.4 +/- 9.8 vs. 119.6 +/- 8.7 ml/min; filtration fraction: 23.2 +/- 1.7 vs. 20.5 +/- 1.6% before and after rosiglitazone, respectively; control subjects: GFR 111.7 +/- 8.6 ml/min, filtration fraction 20.4 +/- 1.5%). Rosiglitazone improved intrarenal NO bioavailability in type 2 diabetes toward control as shown by infusion of L-NMMA. Rosiglitazone reduced albumin excretion in type 2 diabetes with microalbuminuria from 116.5 +/- 31 to 40.4 +/- 12 mg/day. Rosiglitazone ameliorated glomerular hyperfiltration in early type 2 diabetes, improved NO bioavailability, and lessened renal end-organ damage in type 2 diabetes with microalbuminuria.     

Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions

Increased urinary albumin excretion rate is widely accepted as the first clinical sign of diabetic nephropathy. However, it is possible that some diabetic patients could first manifest reduced glomerular filtration rate (GFR) or hypertension. Relatively advanced diabetic renal lesions can be present in some diabetic patients with long-standing normoalbuminuria, and this might indicate increased risk of progression to microalbuminuria and then to overt diabetic nephropathy. The aim of this study was to identify a group of normoalbuminuric type 1 diabetic patients with low GFR and compare them with normoalbuminuric patients with normal GFR. Altogether, 105 normoalbuminuric type 1 diabetic patients with at least 10 years of diabetes duration that had a renal biopsy performed for research purposes were studied. Patients were divided according to GFR into groups with normal (>/=90 ml x min(-1) x 1.73 m(-2)) or reduced (<90 ml x min(-1) x 1.73 m(-2)) GFR. Clinical and renal structural parameters were compared between these two groups. Glomerular structural parameters were estimated by electron microscopic morphometry. The 23 patients with reduced GFR had more advanced diabetic glomerular lesions. The finding of reduced GFR was much more common among female patients, particularly if retinopathy and/or hypertension were also present. This report confirms that reduced GFR occurs among long-standing normoalbuminuric type 1 diabetic patients and is associated with more advanced diabetic glomerular lesions and, probably, with increased risk of progression. For these reasons, we suggest that regular measurements of GFR be performed in long-standing normoalbuminuric type 1 diabetic female diabetic patients, especially in those with retinopathy or hypertension.     

Differential effects of recombinant human growth hormone on glomerular filtration rate and renal plasma flow in chronic renal failure

In normal subjects recombinant human growth hormone (rhGH) increases glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) through the action of insulin-like growth factor-I (IGF-I). We have measured clearance of inulin and para-aminohippuric acid in 18 children with chronic renal failure (CRF) during their 1st year of rhGH treatment to look at the immediate (first 3 h), short-term (1 week) and long-term (1 year) effects of treatment. On day 1 mean (range) age was 9.1 (4.9–13.9) years, GFR 19 (9–58) and ERPF 77 (34–271) ml/min per 1.73 m². During treatment height velocity increased from 4.5 (1.7–6.5) to 9.5 (4.8–12.7) cm/year (P<0.0001). Two children required dialysis after 0.75 years and 1 child was electively transplanted after 0.5 years. There were no other serious adverse events. GFR and ERPF were unchanged in the 3 h following rhGH. GFR remained constant on day 8, 22 (6–56) and after 1 year, 20 (9–59) ml/min per 1.73 m². ERPF increased to 96 (33–276) ml/min per 1.73 m² on day 8P=0.005), and remained elevated, but not significantly so, at 99 (24–428) ml/min per 1.73 m² at 1 year. Fasting IGF-I increased from 147 (46–315) ng/ml to 291 (61–673) by day 8P<0.003), and to 341 (101–786) ng/ml at 1 year. There was no correlation between the change in IGF-I and renal function. Blood pressure, albumin excretion and dietary protein intake were unchanged by treatment. The significance of increased ERPF after 1 week of rhGH in CRF is unclear, but long-term follow-up of renal function is indicated.     

Urinary albumin excretion rate and glomerular filtration rate in the prediction of diabetic nephropathy; a long-term follow-up study of childhood onset type-1 diabetic patients.

BACKGROUND: Predictors of diabetic nephropathy are only partly known. The role of glomerular hyperfiltration is much discussed. We have studied the cumulative incidence of micro and macroalbuminuria and the predictive value of glomerular filtration rate (GFR) and screening value of albumin excretion rate (AER) in type-1 diabetes. METHODS: A cohort of diabetic children was followed up at a mean duration of 29+/-3 years. All 75 children treated in one hospital with diabetes duration > or =8 years were prospectively followed for 8 years examining GFR, AER, blood pressure and HbA1c. After another 8-10 years, 60 of them were traced for endpoint follow-up. RESULTS: Seven patients (12%) developed macroalbuminuria, i.e. persistent overnight AER>200 mg/min, 12 (20%) developed persistent microalbuminuria (AER 15-200 mg/min) and 17 (28%) transient microalbuminuria (>15 mg/min on two consecutive occasions, normalized at endpoint). One baseline screening value of 24-h AER>15 mg/min predicted 93% of patients with persistent micro or macroalbuminuria. The negative predictive value was 78%. Six of seven macroalbuminuric and 10 of 12 microalbuminuric patients had a baseline GFR above the normal limit of the method (> or =125 ml/min/1.73 m(2)). When adjusted for diabetes duration, increased GFR predicted macro or microalbuminuria (odds ratios=5.44, P=0.04). The positive predictive value for having an increased baseline GFR was 53%.The negative predictive value was 77%. Stratification for HbA1c did not change the effect of an increased GFR. CONCLUSIONS: At a mean diabetes duration of 29 years the cumulative incidence of macroalbuminuria was 12%; however, another 20% had persistent microalbuminuria. A screening value of 24-h AER >15 mg/min was a strong predictor, whereas increased GFR was a weaker but significant predictor for micro and macroalbuminuria.     

Long-term prognosis of hemolytic uremic syndrome and effective renal plasma flow

The long-term prognosis of diarrhea-associated hemolytic uremic syndrome (D+ HUS) was evaluated in a cohort of 127 of 149 children who had survived the acute phase. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated by serial ⁵¹Cr-EDTA and ¹²³iodine-hippurate clearances. All children had acute renal failure during the initial phase and 74% of patients were dialyzed. During the 1st year, mean GFR and ERPF increased continuously until a plateau was reached. In the 2nd year after the diagnosis of HUS, GFR was below 80 and ERPF below 515 ml/min per 1.73 m² in 16% and 47% of patients, respectively. At the end of a median follow-up of 5.0 (range 2.0–13.2) years, the proportion of children with renal sequelae such as proteinuria ≥300 mg/l, hypertension, or a GFR <80 ml/min per 1.73 m² was 23%. Anuria of more than 7 days’ duration and hypertension during the acute phase were statistically significant risk factors for an unfavorable outcome. A reduced ERPF in the 2nd year was found in 93% of patients with sequelae. Mean filtration fraction (SD) in these patients was 0.26 (±0.07) versus 0.19 (±0.05) in patients without sequelae (P<0.0001). These data suggest that loss of nephrons during the acute phase may implicate hyperfiltration in the residual functioning kidney mass leading to progressive renal disease. ERPF in the 2nd year after D+ HUS may serve as an excellent parameter to detect patients with a high risk of an unfavorable long-term outcome. Received: 17 September 1998 / Revised: 31 March 1999 / Accepted: 1 April 1999     

Age as a determinant of glomerular filtration rate in non-insulin-dependent diabetes mellitus

BACKGROUND: The level of glomerular filtration rate (GFR) and its determinantsin non-insulin-dependent diabetes mellitus (NIDDM) are currentlycontroversial. DESIGN OF THE STUDY: We measured GFR and effective renal plasma flow (ERPF) in 121consecutive NIDDM without evidence of overt diabetic nephropathy.Age varied from 28 to 70 years, 61.2% were women and known durationof NIDDM was 0–37 years. Hypertension was detected in36.4% of patients and 47.8% had microalbuminuria. RESULTS: An inverse correlation was found between GFR and age, but notwith known duration of NIDDM. It was a weak correlation (r=–0.41)but statistically significant (P<0.001). The other variablesconsidered were not significant by multiple stepwise regressionanalysis, but patients with lower GFR tended to have diabeticretinopathy more frequently. GFR was lower in hypertensive comparedto normo tensive patients (123±28.4 versus 136±32.5ml/min/1.73 m²; P<0.05), but was not different between patientswith normal and elevated albumin excretion rate. ERPF also hadan inverse correlation with age (r=–0.45, P<0.001). CONCLUSION: We conclude that (i) age should be considered as a confoundingvariable when evaluating GFR in patients with NIDDM, and (ii)the age-dependent decline in GFR may mask hyperfiltration inthe early stages of diabetic nephropathy in NIDDM.     

Recovery of Renal Function After Open and Laparoscopic Partial Nephrectomy

Background

Although oncologic outcomes appear to be similar after laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN), data on renal function are lacking.

Objective

To evaluate the change over time in renal function after LPN and OPN.

Design, setting, and participants

We identified 987 patients with a single sporadic tumor and a normal contralateral kidney who were treated by LPN (n = 182) and OPN (n = 805) between January 2002 and July 2009.

Intervention

All patients underwent LPN or OPN at Memorial Sloan-Kettering Cancer Center.

Measurements

Estimated glomerular filtration rate (GFR) was calculated using the abbreviated Modification of Diet in Renal Disease formula. We created a multivariable generalized estimating equations linear model that predicted GFR based on the time from surgery, preoperative GFR, tumor size, American Society of Anesthesiologists score, and ischemia time.

Results and limitations

Mean patient age, tumor size, and ASA score were similar between LPN and OPN patients. The baseline preoperative GFR was lower in the laparoscopic group (67 ml/min per 1.73 m² vs 73 ml/min per 1.73 m²; p < 0.001). The mean ischemia time was shorter after LPN than OPN (35 min vs 40 min, respectively; p < 0.001). In a multivariable model, the interaction term between time from surgery and approach was statistically significant (p = 0.045), indicating that there was a differential effect on recovery of renal function over time by approach. Laparoscopically treated patients maintained a slightly higher renal function than those treated via an open approach. The 2-mo and 6-mo predicted GFR for a typical patient increased slightly from 65 ml/min per 1.73 m² to 67 ml/min per 1.73 m², respectively, for those treated laparoscopically but remained constant at 62 ml/min per 1.73 m² after OPN.

Conclusions

Our data suggest that the surgical approach has a small effect on the recovery of renal function after partial nephrectomy. Laparoscopically treated patients maintained slightly higher renal function.     

Cyclosporine-A-induced nephrotoxicity in children with minimal-change nephrotic syndrome: long-term treatment up to 10 years

The impact of cyclosporine A (CsA) therapy in patients with steroid-dependent nephrotic-syndrome (SDNS) on long-term renal function is controversial. Data beyond 5 years are rare. Long-term renal function was evaluated in children with SDNS with and without CsA therapy, especially beyond 5 years. Twenty children were treated with CsA (study group) for a mean of 5.4 ± 2.2 years (ten patients for 5–11 years). Glomerular filtration rate (GFR) was calculated before and after 3 and 12 months and at latest follow-up of therapy. Fifteen children with cyclophosphamide-treated SDNS without CsA served as controls. In the study group, GFR decreased within 12 months from 136 ± 19 to 120 ± 31, to 114 ± 14 ml/min per 1.73 m² at latest follow-up (p < 0.0001). Patients with CsA > 5 years had a GFR of 111 ± 14 ml/min per 1.73 m² at latest follow-up without a GFR below 90 ml/min per 1.73 m². No CsA toxicity was found in biopsies. In the control group, GFR dropped within 3 months, from 137 ± 27 to 130 ± 24, to 126 ± 19 ml/min per 1.73 m² at latest follow-up (p = 0.1). Patients with and without nephrotoxic CsA therapy showed a drop in GFR. In CsA-treated patients, GFR was about 12% lower at latest follow-up compared with patients without nephrotoxic therapy but always remained within normal range. CsA seems to be safe, even in long-term treatment for more than 5 years.