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 m(2) stop), whereas renal plasma flow was significantly lower (463.7 +/- 103.9 vs. 587.2 +/- 105 ml/min per 1.73 m(2) , 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 m(2) stop). 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

Distal nephron sodium-potassium exchange in children with nephrotic syndrome

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ARF in children with minimal change nephrotic syndrome may be related to functional changes of the glomerular basal membrane

ARF in children with minimal change nephrotic syndrome may be related to functional changes of the glomerular basal membrane. Vande Walle J, Mauel R, Raes A, Vandekerckhove K, Donckerwolcke R. Department of Pediatric Nephrology, University of Gent, Belgium. BACKGROUND: Acute renal failure (ARF) is a rare complication in children with minimal change nephrotic syndrome (MCNS). Several etiologic factors (renal vein thrombosis, side effect of such drugs as nonsteroidal anti-inflammatory drugs, and infections) have been described, but often such conditions are lacking, and hemodynamic derangements or changes in glomerular permeability are suspected. METHODS: We assessed the role of alterations in renal perfusion and glomerular permeability by measuring clearances of inulin and para-aminohippurate before and during intravenous administration of a 20% albumin solution in patients with MCNS and oliguric ARF (serum creatinine > 1 mg/dL [88 micromol/L], urine output < 0.5 mL/kg body weight/h). RESULTS: Eleven patients aged 2.5 to 15 years with biopsy-proven MCNS were studied. Before albumin administration, all patients had a significantly decreased glomerular filtration rate (GFR), whereas most renal plasma flow (RPF) values were within the normal range. This resulted in a significantly decreased filtration fraction (FF; GFR/RPF x 100), which was extremely low (<7%) in 4 patients. There was a heterogeneous response to albumin administration. Albumin infusion tended to increase RPF, but changes did not reach statistical significance. Some patients showed an increase in glomerular filtration, whereas in others, it decreased. In 7 patients, FF remained unchanged or decreased even further. CONCLUSION: Our data suggest that, although in some patients decreased intravascular volume may contribute to reduced renal function, changes in glomerular permeability may have a major role in ARF occurring in uncomplicated MCNS

Evidence of Partial Anti-Enuretic Response Related to Poor Pharmacodynamic Effects of Desmopressin Nasal Spray

Purpose: Desmopressin is an evidence-based medicine level 1, category A therapy for monosymptomatic nocturnal enuresis. However, in up to 40% of patients only partial desmopressin response is obtained. While the poor pharmacokinetic characteristics of the different available formulations may have a role in apparent therapy resistance, there are limited data available to support this theory. We sought to identify pharmacodynamic factors involved in partial desmopressin response or desmopressin resistance in children with monosymptomatic nocturnal enuresis, with special emphasis on concentrating performance, and time to reach and duration of maximal urine concentration. Materials and Methods: We evaluated 64 children with monosymptomatic nocturnal enuresis and proved nocturnal polyuria lacking full response to desmopressin treatment. The study involved 2 separate home based test days (A and B), each consisting of 9 timed urine collections starting in the evening 1 hour before desmopressin administration and continuing for 16 hours following desmopressin administration. Test A was done during fluid restriction, and test B was done during an oral fluid load. Results: Under fluid restriction 16 patients failed to achieve urine concentration greater than 850 mOsmol/l at the midnight collection following desmopressin administration. After an oral fluid load given at the start of the test the majority of patients failed to reach maximal concentration of urine as voided during hydropenia, and 45 patients failed to regain appropriate dilution of urine even when an oral water load of 15 ml/kg (urine osmolality less than 750 mOsmol/l) was given in the morning at the end of the test. This finding is suggestive of a prolonged duration of action of the drug. Conclusions: Pharmacodynamic tests reveal a suboptimal effect of desmopressin on urine concentration in a significant percentage of patients, which worsens when fluid is not restricted before desmopressin administration. Also the time to reach maximal antidiuretic effect and the duration of pharmacodynamic action show a wide range, requiring individualization of mode and time of administration. Our data demonstrate that a simple pharmacodynamic test as described may give important information on time of dosing, duration of action and influence of oral fluid intake, allowing individualization of therapy. Data also reveal that desmopressin should be administered at least 1 hour before bedtime, and that in case of therapy resistance a longer interval, up to 2 hours, might further reduce diuresis rate in the early night. Because of the documented prolonged action of desmopressin in some patients, increasing the dose without performing pharmacodynamic testing is no longer acceptable

Hypercalciuria is related to osmolar excretion in children with nocturnal enuresis

Purpose: We evaluated the incidence of hypercalciuria, defined as urinary calcium-to-creatinine ratio greater than 0.21 mg/mg, in children with nocturnal enuresis, and the association with concurrent values of diuresis and osmolar excretion. Materials and Methods: A total of 550 children admitted to a tertiary university center were included in the study. A 24-hour urine collection was performed in 8 sampling periods for measurement of calcium excretion, osmolality and diuresis. Results: Of the children with nocturnal enuresis 12% had 24-hour hypercalciuria. Up to 29% of the timed urine samples exhibited hypercalciuria. There was a significant correlation between calcium excretion and nocturnal diuresis volume (polyuria), low urinary osmolality, and increased sodium and osmolar excretion of nighttime urine samples (all p < 0.001). Conclusions: Patients referred to a tertiary enuresis center have a high incidence of hypercalciuria. However, the significant correlation between hypercalciuria and osmolar excretion and diuresis suggests that it is a comorbid factor rather than a primary pathogenic factor. As such, we cannot confirm the data from Italian studies relating nocturnal enuresis to primary hypercalciuria, and suggest instead an association with nutritional intake

Partial response to intranasal desmopressin in children with monosymptomatic nocturnal enuresis is related to persistent nocturnal polyuria on wet nights

Purpose: The anti-incontinence effect of desmopressin resides in its concentrating capacity and antidiuretic properties. We compared nighttime urine production on wet and dry nights in a highly selected study population of children with monosymptomatic nocturnal enuresis associated with proved nocturnal polyuria who responded only partially to intranasal desmopressin. Materials and Methods: We retrospectively analyzed 39 home recordings of nocturnal urine production and maximum voided volume in children 7 to 19 years old (median 8.9) with monosymptomatic nocturnal enuresis with nocturnal polyuria who had a partial response to desmopressin. Nocturnal diuresis volume and maximum voided volume were documented at baseline (14 days) and during 3 months of followup. Results: Baseline nocturnal urine output (439 +/- 39 ml) was significantly higher than the maximum voided volume (346 93 ml, p <0.01). During desmopressin treatment nocturnal urine output on wet nights (405 +/- 113 ml) differed significantly from that on dry nights (241 +/- 45 ml). During treatment nocturnal urine output on wet nights did not differ from baseline values. Conclusions: Persistence of nocturnal polyuria on wet nights in partial desmopressin responders may be related to an insufficient antidiuretic effect. In addition to poor compliance and suboptimal dosing, the poor bioavailability of intranasal desmopressin may be a pathogenic factor. Further prospective studies are needed

Nocturnal polyuria is related to absent circadian rhythm of glomerular filtration rate

Purpose: Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria. Materials and Methods: We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria. Results: Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate. Conclusions: Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions