Comparison of cystatin C- and creatinine-based glomerular filtration rate formulas with inulin clearance in pediatric renal transplantation.

BACKGROUND: It has been suggested that plasma cystatin C (Cyst-C) concentrations provide better indicators of changes in glomerular filtration rate (GFR) than plasma creatinine concentration (PCr). METHODS: We compared the performance of five equations--2009 Schwartz, Local Schwartz, Larsson, Le Bricon, and Schwartz Combined--in 60 renal transplant children by calculating the mean bias, Pearson correlation coefficient (R) and determination (R2), 10% (P10) and 30% (P30) accuracies, and Bland-Altman plots. GFR was measured by inulin clearance. RESULTS: For the whole population, R2 was slightly lower for formulas based on Cyst-C or PCr, but the mean bias was lower, and P10 and P30 were greater, than using combined Schwartz equation. However, the mean estimated GFR by Schwartz 2009, Local Schwartz, and Schwartz combined equations was not statistically different from the mean inulin clearance measurement. CONCLUSIONS: In our pediatric transplant population, the combined Schwartz formula exhibited better performance to estimate GFR than formulae based on Cyst-C or combined PCr.

Kidney graft outcome and quality (after transplantation) from uncontrolled deceased donors after cardiac arrest.

The use of uncontrolled deceased donors after cardiac arrest (uDDCA) has been developed in France to compensate for organ shortage. The quality of these kidneys remains unclear. We analyzed kidney graft function and histology from 27 uDDCA and compared them with kidneys from 30 extended criteria donors (ECD) and from 24 simultaneous pancreas kidney (SPK) donors as a control group of optimal deceased donors. Kidneys from ECD and SPK donors were preserved by static cold storage while kidneys from uDDCA were preserved by pulsatile perfusion. The uDDCA graft function at 3 years posttransplantation (estimated with MDRD and measured with inulin clearance) did not differ from that of the ECD group (eGFR 44.1 vs. 37.4 mL/min/1.73 m(2) , p = 0.13; mGFR 44.6 vs. 36.1 mL/min/1.73 m(2) , p = 0.07 in the uDDCA and ECD groups, respectively). The histological assessment of 3-month and 1-year protocol biopsies did not show differences for interstitial lesions between the uDDCA and ECD grafts (IF score at M3 was 30 vs. 28% and at M12 36 vs. 33%, p = NS). In conclusion, the results at 3 years with carefully selected and machine-perfused uDDCA kidneys have been comparable to ECD kidneys and encourage continuation of this program and development of similar programs.

Chronic dehydration may impair renal function in patients with chronic intestinal failure on long-term parenteral nutrition.

BACKGROUND & AIMS: Renal impairment is a documented complication in long-term parenteral nutrition (LTPN) patients. However, the aetiologies have remained elusive. The aim of this study was to evaluate the impact of parenteral nutrition, digestive status, and hydration level on renal function in LTPN patients. METHODS: In a prospective study of 40 LTPN patients, renal function and hydration level were assessed by measurement of inulin and creatinine clearances, plasma creatinine, urea, aldosterone and renin and urinary sodium/potassium ratio. Patients were assigned to one of two groups according to their inulin clearance (normal = Group 1, 20% decrease or more = Group 2). RESULTS: Of the patients, 52.5% (21/40) had a decrease in glomerular filtration rate (-38 +/- 15%), with age taken into consideration. Patient characteristics, parenteral nutrition composition or duration and intestinal status were not different between the two groups. Urologic or nephrologic diseases were more frequent in Group 2 patients. Moreover, in Group 2 patients, a urinary sodium/potassium excretion ratio of less than 1 in 8/21 patients and plasma renin (316 +/- 298 vs. 86 +/- 53% of normal value) and aldosterone (291 +/- 464 vs. 58 +/- 36 pmol/l) that were significantly higher than in Group 1 patients suggested a hypovolemic component. CONCLUSION: Decreased renal function is frequent (52.5%) in LTPN patients. A volemic component was associated in more than 70% of them. An elevation of serum creatinine or an inversion of the urinary Na/K ratio requires an evaluation of hydration equilibration and an oral rehydration and a modification in parenteral nutrition formulation.

[Improving the interlaboratory variation for creatinine serum assay]. / Dosage de la créatininémie en 20003: état des lieux analytique et essai de standardisation de l'étalonnage.

PURPOSE: To assess inter-assay variation and accuracy of blood creatinine measurements as well as the effect of the standardization of the calibration procedures on inter-assay variation. METHODS: Inter-assay variation and accuracy were assessed using 30 frozen human sera and 3 certified reference materials, which were analysed by 17 creatinine assays (colorimetric: 12, enzymatic: 4, HPLC: 1). Usual calibration procedure was compared with two common calibration procedures using either a reference material (404.1 micromol/L), or secondary sera calibrators (69, 115 et 180 micromol/L). RESULTS: Most of the commercially available methods display inaccuracy, > 10% for creatininemia < 150 micromol/L in most cases. For this concentration range, the mean creatininemia was statistically significantly different as a function of the assay used (p < 0.001). Enzymatic assays produced lower results than colorimetric ones for low creatinine levels but higher results for high creatinine levels. Assays being calibrated according to the manufacturer's recommendations, the median dispersion factor was 14% for the 20 samples between 45 and 150 micromol/L, and 8% for the 10 samples between 250 and 350 micromol/L. The calibration procedure modified inter-assay variation significantly (p < 0.001) but we gained little advantage from both common calibration procedures. A significant decrease of inter-assay variation occurred within each technical group (colorimetric or enzymatic) when a common calibration was performed using calibrators which concentration(s) was(were) close to the concentrations to be measured. CONCLUSIONS: Inter-assay variation is too high to allow prediction of glomerular filtration rate (GFR) or creatinine clearance from serum creatinine level. Our results highlight the interest of a calibration procedure using several concentrations with at least one between 90 and 150 micromol/L. The marketing of such a calibrator should be considered in order to decrease inter-assay variation in the range of creatinine levels which defines a mild chronic renal failure. Such an approach will certainly reduce inter-assay variation only within each technical group but could allow to include technical group as a co-variable in the algorithms developed for predicting GFR or creatinine clearance. A global transferability will certainly need the correlation of all types of creatinine assays versus a definitive method, whom definition remains uncertain.

[Target organ effects in untreated hypertension]. / Atteinte des organes cibles dans l'HTA jamais traitée.

The parallel investigation of the renal and cardiac complications of recent and never treated systemic hypertension has only rarely been undertaken. The aim of this study was to define the renal function of never treated hypertensive subjects, separated into white coat hypertensives (HTbb: n = 19, BP at consultation 153/97 mmHg) or permanent hypertensives (HT: n = 49, BP at consultation 169/104 mmHg) as a function of their 24 hour BP. Their renal functions were then compared with those of normotensive subjects (NT: n = 10). The 68 hypertensive subjects seen consecutively underwent renal function investigation (DFG: glomerular filtration rate, DPR: renal plasmatic debit, and muAlb: microalbuminuria over 24 hours), and myocardial echography (measurement of the left ventricular mass index, IMVG). The white coat hypertensives had a normal renal function, while the permanent hypertensives had a significant decrease in DPR and a significantly higher muAlb compared to the normotensives. Compared to the white coat hypertensives, the permanent hypertensives had a significantly lower DFG and DPR, as well as a higher muAlb and IMVG. In all the hypertensives (white coat and permanent) the 24 hour systolic BP was significantly correlated with muAlb (r = 0.51, p < 0.001), filtration fraction (r = 0.30, p < 0.05), and IMVG (r = 0.52, p < 0.001). The renal and myocardial parameters were not significantly correlated. In conclusion, there seems to be a continuum between the level of ambulatory BP and the effect on target organs without a parallel progression of the renal and myocardial effects. From a practical point of view, only ambulatory BP measurement allows differentiation of permanent hypertensives who have a very early renal and/or myocardial effect, while white coat hypertensives are spared.

Fading renal hyperfiltration in children following liver transplantation.

In a prospective longitudinal study, we investigated the renal function (RF) of 23 children before and after orthotopic liver transplantation (OLT). The aim was to assess both the outcome of pretransplant hyperfiltration and the clinical nephrotoxic effects of cyclosporin A (CsA); children with decreased RF prior to OLT were therefore excluded. The RF study of the 13 remaining patients included glomerular filtration rate (GFR) and effective renal plasma flow (RPF) measured by inulin (Cin: mL/min/1.73 m2) and para-amino hippurate (Cpah: mL/min/1.73 m2) clearances, respectively. Hyperfiltration prior to OLT was observed in six children, i.e. Cin>170 [range 172-230] and Cpah>800 [808-1,133]. A significant decrease in RF was noted as soon as 6 months after OLT: Cin (mean+/-SD)=107+/-23 vs. 158+/-46 (p<0.003); Cpah=583+/-119 vs. 791+/-243 (p<0.004). This was due to loss of hyperfiltration in the six children, as there was no significant difference in RF before and 6 months after OLT in the other seven children. With a 36-month follow-up, there was no correlation between CsA trough blood level and RF. In conclusion, following OLT, RF underwent early changes owing to loss of prior hyperfiltration in children without impaired RF before OLT. In addition, no evidence of CsA nephrotoxicity was found and RF remained stable during follow-up.

Vesicoureteral reflux after kidney transplantation in children.

BACKGROUND: The prevalence and significance of vesicoureteral reflux (VUR) after kidney transplantation in adults varies between authors and there have been few reports in children. METHODS: We conducted a retrospective study in a single-centre paediatric cohort. Fifty-five of the 84 children who underwent kidney transplantation over a 5-year period were checked with routine cystography after a median of 8 months post-transplantation. Graft function and urinary-tract infections were assessed during the first 6 years after transplantation. RESULTS: VUR into the graft was present in 58% of the patients. Graft function and incidence of urinary-tract infections were similar in the two groups, independent of VUR. After having excluded infections attributed to the presence of a catheter, actuarial survival rates without pyelonephritis and without pyelonephritis following a first lower urinary-tract infection were worse in patients with VUR (P:=0.017 and P:=0.0039 respectively). None of the eight patients with VUR treated with antibiotic prophylaxis after a first acute pyelonephritis (APN) episode presented subsequent APN after 4.4+/-3.3 years on therapy. CONCLUSIONS: VUR to the graft occurred in more than half paediatric renal transplant recipients. This condition was associated with an increased risk of APN. Long-term antibiotic prophylaxis seems to be able to prevent APN in transplanted children with VUR.

Renal function of children exposed to cyclosporin in utero.

BACKGROUND: The use of cyclosporin (CsA) has improved graft survival in transplant (Tx) patients despite its potential nephrotoxicity. Children born to transplanted women may present with intrauterine growth retardation (IUGR). On the basis of potential reduced nephron mass both in IUGR and in newborn experimental animals exposed to CsA in utero, we investigated the renal function of children >1 year of age born to women under maintenance immunosuppression, including CsA. METHODS: Fourteen children born to 12 Tx women (nine kidney, one pancreas-kidney, one heart, one liver) were investigated using inulin clearance (C(in)), para-aminohippuric acid clearance (C(PAH)), microalbuminuria, and electrolyte reabsorption rate. RESULTS: Gestational age of the 14 infants was 34+/-3 weeks and birth weight 2018+/-620 g. During pregnancy, CsA trough blood level was 234+/-115 microg/l and plasma creatinine range was 96-136 micromol/l. Two children were excluded from the study because renal investigation led to a diagnosis of hereditary nephritis (one Alport syndrome, one familial dominant focal segmental glomerulosclerosis) that was retrospectively completed in the mother. Renal function tests were finally performed in 12 children at 2.6+/-1.8 years of age: BP 94+/-7/55+/-5 mmHg, C(in) 117+/-28 ml/min/1.73 m(2), C(PAH) 545+/-124 ml/min/1.73 m(2), filtration fraction 0.23+/-0.03, microalbuminuria 4.2+/-3.5 mg/mmol. Electrolyte tubular reabsorption rates and urine concentrating capacity were normal. CONCLUSION: These results suggest that in children born to transplanted women taking CsA, renal function develops normally despite prolonged exposure in utero.

Renal function and urinary excretion of electrolytes in patients receiving cyclic parenteral nutrition.

BACKGROUND: Long-term parenteral nutrition (LTPN) has been shown to induce renal impairment and bone demineralization. However, the mechanism of both injuries has not been clarified. METHODS: This prospective study was performed in 16 patients with short bowel syndrome, aged 28 to 63 years, who had received LTPN for 31 +/- 7 months. Urinary excretion of electrolytes were measured before (diurnal, 12 hours) and during (nocturnal, 12 hours) parenteral nutrition. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured in the morning after the nutritional bag supply. RESULTS: Mean GFR was 86 +/- 7 mL/min/1.73 m2 and ERPF was 412 +/- 31 mL/min/1.73 m2. Decreased GFR was present in 9 patients. There was no relation between renal function and age or the duration of LTPN. Urine volume and excretion of urea, creatinine, sodium, magnesium, and phosphate but not potassium increased significantly in nocturnal urine compared with diurnal urine. On the basis on 24-hour calciuria, 7 patients were normocalciuric (NCa) whereas 9 were hypercalciuric (HCa). Both had excessive nocturnal calciuria, but only the HCa group had diurnal hypercalciuria, the calcium supply being identical. Bone mineral density (BMD) was slightly, although not significantly, higher in NCa group, but in all patients BMD correlated significantly with calciuria. Serum parathyroid hormone and vitamin D were not different in the two groups. CONCLUSIONS: In patients receiving LTPN, renal function is frequently impaired, by a mechanism which remains unclear. In nocturnal cyclic mode of nutrition, urinary volume and electrolyte excretion occurred predominantly during the infusion, but some patients have diurnal hypercalciuria. In these patients a defect in renal calcium reabsorption or more likely the inability of bone to retain the infused calcium may be responsible for bone demineralization.

Mycophenolate mofetil reduces myofibroblast infiltration and collagen III deposition in rat remnant kidney.

BACKGROUND: Myofibroblasts have been shown to play a pivotal role in the synthesis of extracellular matrix components in several animal models of renal fibrosis. The purpose of the present study was to investigate whether mycophenolate mofetil (MMF) reduces interstitial myofibroblast infiltration and collagen III deposition in 5/6 nephrectomized rats. METHODS: Forty-five Wistar rats underwent 5/6 renal ablation and received by daily oral gavage either vehicle (N = 20) or MMF (N = 25) during the 60 days following surgery. Groups of five treated and five untreated rats were killed at two, four, and eight weeks after subtotal nephrectomy. Four untreated and three treated rats were killed at week 12, one month after treatment withdrawal. At the time of sacrifice, proteinuria, plasma, and urine creatinine were determined. Immunohistochemistry was performed on renal tissue for alpha-smooth muscle actin (alpha-SMA), a cytoskeletal marker of myofibroblasts, for type III collagen, and for proliferating cell nuclear antigen (PCNA). Moreover, in order to study the in vitro effects of MMF on fibroblast proliferation, rat fibroblasts were cultured in the presence or absence of mycophenolic acid (MPA). RESULTS: At all periods studied, MMF treatment improved renal functional parameters and progressively decreased remnant kidney hypertrophy and glomerular volume increment. Proliferating cells in renal tubules, interstitium, and glomeruli, as well as interstitial myofibroblast infiltration and interstitial type III collagen deposition, were also significantly reduced by MMF treatment. In addition, MPA exhibited a dose-dependent inhibitory effect on in vitro proliferation of rat fibroblasts. CONCLUSION: Reduction of interstitial myofibroblast infiltration may be an important event by which MMF significantly prevents renal injury following subtotal renal ablation. Thus, our results suggest that MMF could be useful to limit the progression of chronic renal disease toward end-stage renal failure.

Interstitial alpha-smooth muscle actin: a prognostic marker in membranous nephropathy.

AIM: Membranous nephropathy in adults causes 20% of nephrotic syndromes. Spontaneous outcome of this glomerulopathy is difficult to evaluate from clinical and histological data. Some patients can achieve complete remission, while others develop progressive renal failure. In this study we assessed alpha-smooth muscle actin (alpha-SMA) expression in renal interstitial myofibroblasts as a marker to predict the outcome of membranous nephropathy. PATIENTS AND METHODS: Renal function tests in tandem with alpha-SMA immunolabelling were performed on 25 patients with a mean follow-up of 7.2+/-5.6 years. The intensity of interstitial alpha-SMA (ialpha-SMA) immunostaining was compared to changes in glomerular filtration rate (GFR) evaluated by inulin clearance, between the time of diagnosis (GFR1) and the end of follow-up (GFR2). RESULTS: A significant correlation (r = 0.62, p<0.001) was found, between the intensity of interstitial myofibroblasts, immunolabeling and GFR at the end of follow-up. Moreover, the annual GFR variation and the annual percentage of GFR variation were correlated to interstitial myofibroblast labeling (respectively r = 0.62, p<0.001; r = 0.67, p<0.001). In addition, the importance of proteinuria, initial GFR impairment and fibrosis were confirmed as prognostic criteria. CONCLUSION: This study strongly shows that ialpha-SMA expression is a useful and early prognostic marker in the evolution of membranous nephropathy.

[Graft function following renal transplantation in children]. / Evolution de la fonction du greffon après transplantation rénale chez l'enfant.

BACKGROUND: Since renal transplantation is known to be the best choice for the growing child with end-stage renal failure, we prospectively evaluated early and late graft function in transplanted children. POPULATION AND METHODS: The study included 78 children (32 girls, 46 boys) 10.4 +/- 0.6 years at the time of transplantation. Renal investigations were performed at 3, 6 and 12 months post-transplantation and yearly thereafter. Inulin clearance was used to evaluate the glomerular filtration rate (GFR), and the reabsorption rates of Na, P and Ca were measured concomitantly. RESULTS: The overall adjusted GFR was approximately 70 mL/min/1.73 m2 and remained unchanged during the first 5 years post-transplantation. In the mean time the absolute GFR increased significantly, suggesting a remaining capacity for compensatory hypertrophy of the transplanted kidney. Renal function was significantly influenced by the number of rejection episodes during the first 2 years post-transplantation but no correlation was found between GFR and the number of HLA mismatches or the use of preemptive transplantation.

Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma.

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD) years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2, ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.

Role of the donor in post-transplant renal function.

BACKGROUND: The donor, i.e. adult or paediatric, might influence the outcome of the graft function. METHODS: The glomerular filtration rate (GFR) of 120 transplanted children (47 girls) aged 10.4+/-4.6 years (0.7-17.2) was prospectively assessed over a 5-year period. The patients were divided into two groups according to the age of donor: adult (donor age > 18 years; n=33) and paediatric (donor age < 18 years; n=87). GFR was assessed by inulin clearance at 3, 6 and 12 months and yearly thereafter. RESULTS: The average GFR was stable in the range of 70 ml/min/1.73 m2 for the whole follow-up period. The adjusted GFR in adult graft recipients was significantly higher at 3 months post-transplantation: 80.6+/-36.9 vs 65.1+/-22.0, P=0.02. However, from the second year post-transplantation, the adjusted GFR in paediatric graft recipients became significantly higher than that of adult graft recipients. Such results could be due to an improvement in the absolute GFR (ml/min) of paediatric graft recipients with time (P=0.0001) whereas that of the adult graft recipients remained stable despite the children's growth. CONCLUSIONS: The adjusted GFR of adult graft recipients was significantly higher than that of paediatric graft recipients in the early post-transplant period. In the long-term, a progressive decrease in adjusted GFR was noted in adult graft recipients. On the one hand, this may be due to a functional adaptation and/or inadequate compensatory growth of the graft. On the other hand, the absolute GFR of paediatric graft recipients increased, suggesting an ongoing capacity for growth and/or compensatory hypertrophy after child-to-child renal transplantation.

Outcome of preemptive renal transplantation and pretransplantation dialysis in children.

The present study compares the outcome of 40 children (39%) transplanted without prior dialysis, i.e., preemptive transplantation (PET), with 63 children (61%) transplanted after a variable duration of dialysis, i.e., pretransplantation dialysis (PTD). The two groups were matched for recipient and donor age and for immunological risk factors. There was no statistical difference in the time to first acute rejection episode nor in the number of acute rejection episodes during the 1st year after renal transplantation. In the PET group, 78% of the recipients received blood transfusion versus 92.5% in the PTD group (P < 0.05), and the average number of blood units per patient was 3.2 and 7.8, respectively (P < 0.05). Arterial hypertension was found in 55% of the patients in the PET group versus 73% in the PTD group (P < 0.05). The number of functioning grafts at the end of the study period was 87.5% in the PET group and 73% in the PTD group (NS). The major cause of graft failure was vascular thrombosis in the PET group (3/5) and chronic allograft rejection in the PTD group (10/17). In the PET group, the actuarial graft survival rate was 100%, 84%, 81%, and 76% at 1, 3, 5, and 7 years, which was not statistically different from the PTD group at 1, 3, and 5 years (98%, 91%, and 73%, respectively) but there was a significantly lower graft survival (59%) after 7 years in the PTD (P < 0.05). The 7-year actuarial patient survival rate was 97% in the PET group and 90% in the PTD group (NS). In the PTD group, children on dialysis for less than 1 year (group 1, n = 25) were compared with those on dialysis for more than 1 year (group 2, n = 38). Arterial hypertension was noted in 40% of patients from group 1 and 65% from group 2 (P < 0.05); there was no significant difference in graft loss rate. In conclusion, these results confirm PET as the preferred approach rather than PTD in children who need renal replacement therapy.

[Renal function after nephrectomy for Wilms' tumor]. / Fonction rénale après néphrectomie pour tumeur de Wilms.

BACKGROUND: Most children with Wilms tumour recover after nephrectomy, chemotherapy and sometimes radiotherapy. It is therefore important to assess their long-term renal function. POPULATION AND METHODS: Thirty-three patients with Wilms tumour experienced unilateral nephrectomy between 1986 and 1993: three were excluded; 23 were staged as grade I, one at grade II, two at grade III and four at grade IV. They were treated with SIOP 6 and SIOP 9 protocols. The results were compared to five controls who underwent unilateral nephrectomy including three for renal trauma. The glomerular filtration rate (GFR) was measured by inulin clearance and the renal plasma flow (RPF) by para-amino-hippuric acid clearance. RESULTS: The mean age at nephrectomy was 3.4 +/- 2.5 years (median: 3, range: 0.2-10.6) and the duration of follow-up was 4.6 +/- 3.1 years (median: 4.5, range: 1-8.5), the GFR was 93 +/- 13 mL/min/1.73 m2 (median: 93, range: 73-130), the RPF was 441 +/- 85 mL/min/1.73 m2 (median: 453, range: 236-650) and the filtrated fraction (FF) was 0.21 +/- 0.03 (median: 0.20, range: 0.18-0.31). The difference in renal function between patients and controls was not significant (GRF: 86 +/- 12 mL/min/1.73 m2, RPF: 486 +/- 185 mL/min/1.73 m2, FF: 0.22 +/- 0.03). The electrolyte reabsorption rate was normal and none of the patients suffered from arterial hypertension. Fourteen children had urinary albumin: creatinine ratio > 2 g/mol. When comparing patients according to the duration of follow-up after nephrectomy (< 4 years vs > 4 years), the renal function was not statistically different. The age at nephrectomy (< 2 years vs > 2 years) did not increase the risk of renal impairment. CONCLUSION: Children with Wilms tumour who were treated with nephrectomy and non-nephrotoxic drugs (actinomycin, vincristine, epiadriamycin) have a good long-term renal outcome. It is speculated that systematic renal investigation should be limited to those children with increased microalbuminuria and/or elevated blood pressure.

Nifedipine improves recovery function of kidneys preserved in a high-sodium, low-potassium cold-storage solution: study with the isolated perfused rat kidney technique.

BACKGROUND: Extracellular types (high-Na) of cold-storage solution (CSS) have been shown to be more effective in preserving kidneys than intracellular CSS (high-K). On the other hand, calcium entry blockers (CEB) have been demonstrated to improve graft function when administered after and/or prior to transplantation. The ischaemia reperfusion syndrome involves, in part, an alteration in intracellular calcium metabolism that induces an increase in renal vascular resistances (RVR) and other cellular dysfunction, and high-K CSS per se are vasoconstrictive. Since CEB act via a modification in intracellular calcium metabolism on vascular smooth muscle, glomerular, and tubular cells, we evaluated the actual benefit on CEB on kidneys preserved in Belzer's CSS (K-UW) and a high-Na version of Belzer's CSS (Na-UW). METHOD: The isolated perfused rat kidney (IPK) was used, first as a vascular bed to test the effects of CSS on RVR, and the influence of nifedipine. Second, the recovery function of the IPK was assessed by GFR and tubular Na reabsorption, after 24 h preservation in K-UW and Na-UW, with or without nifedipine. Results were compared with a control group in which renal function was measured without prior cold-storage. RESULTS: K-UW but not Na-UW induced an increase in RVR when flushed into the kidney. This vasoconstriction is prevented by nifedipine. K-UW CSS was more deleterious to renal function than Na-UW. Addition of nifedipine to the flush, the CSS for 24 h, and to the normothermic reperfusate further improved recovery function of the IPK cold stored in Na-UW but not in K-UW, without any modification of RVR. CONCLUSION: Nifedipine may be of potential effect in attenuating ischaemic injury by a mechanism which does not involve its vasodilatory properties.