Renal functional reserve in children with a previous episode of haemolytic-uraemic syndrome

Renal function [creatinine clearance (C _Cr)] and renal functional reserve (RFR) was measured in 16 children who had had haemolytic-uraemic syndrome (HUS) an average of 6.6±0.72 years previously. All patients had normal plasma creatinine and blood pressure and only 3 had proteinuria, which was mild in every instance. Patients were studied whilst ingesting three diets which provided an average of 1.5, 2.1 and 3.1 g protein/kg body weight per day, respectively. Diets were administered over three consecutive periods of 7 days each andC _Cr was measured on the 7th day of each diet. Values tended to correlate with protein intake. They were in the normal range when patients were taking 1.5 and 2.1 g protein diets and increased markedly in 13 of the 16 patients (P<0.001) when they ingested the high-protein diet (3.1 g). The effect on glomerular filtration rate (GFR)-measured byC _Cr and inulin clearance (C _in)-of an acute oral protein load was studied in 12 of the HUS patients and four control subjects. In the control periods, prior to the protein load, values forC _Cr were similar in the HUS and control subjects (104.0±11.0 vs 121.6±10.1 ml/min per 1.73 m², NS). HoweverC _in values were significantly reduced in HUS patients (59.5±9.2 vs 102.7±12.4 ml/min per 1.73 m², (P<0.025). TheC _Cr/C _in ratio in the patients averaged 2.10 compared with 1.13 in controls. Acute protein loading was accompanied by an increase inC _in in all controls but in only 8 of the 12 patients. Baseline values forC _in did not correlate with the presence or absence of protein-stimulated enhancement ofC _in. TheC _Cr/C _in ratios after protein loading remained twice as high in HUS patients as in controls. The data indicate thatC _Cr is not an accurate indicator of GFR in children who have had acute renal injury. Tubular secretion of creatinine represents a greater proportion of excreted creatinine in these children, may maintain serum creatinine in the normal range and mask the decrease in GFR. The study also emphasizes the problems of measuring RFR in these children.     

Renal functional reserve and renal hemodynamics in hypertensive patients

The renal functional reserve (RFR) is the ability of the kidneys to increase renal plasma flow and glomerular filtration rate (GFR) in response to protein intake. It is a measure of functional and anatomic integrity of nephrons. It is not known what relation between RFR and kidney Doppler parameters. We aimed to study the relation between the RFR and renal hemodynamic parameters in hypertensive patients with and without nephropathy who had normal kidney function. Twenty-four hypertensive subjects with nephropathy (HTN-n, n?=?10) and hypertension without nephropathy (HTN, n?=?14) were included in the study. Control group included 11 healthy subjects. Baseline GFR (GFR1) and GFR after intake of egg protein 1?mg/kg of body weight were determined (GFR2). RFR was calculated by the following formula: (GFR2-GFR1)/GFR1?×?100%. Doppler ultrasonography was performed. Arterial blood pressure (BP), body mass index (BMI), and estimated GFR were also recorded. HTN and HTN-n groups had impaired levels of RFR compared with controls (p?<?0.05), significantly decreased value of flow velocity parameters (Vmax, Vmin), and increased RRI compared with controls. There was significant negative correlation of RFR with blood pressure levels (sBP, r?=??0.435, p?=?0.009; dBP, r?=??0.504, p?=?0.002), RRI (r?=??0.456, p?=?0.008), micro albuminuria (MAU, r?=??0.366, p?=?0.031) and positive correlation with Vmax and Vmin (r?=?0.556, p?=?0.001 and r?=?0.643, respectively, p?<?0.001). Linear regression showed that RRI and MAU were independent predictors of decreased RFR. RFR is lower in hypertensive patients despite near-normal level of kidney function and is related to particular level of BP. RRI and MAU were independent predictors of decreased RFR.     

Assessment of maximal tubular phosphate reabsorption: comparison of direct measurement with the nomogram of Bijvoet

It is well established that plasma phosphate (Pp) is largely determined by the renal phosphate threshold, which is best described by the maximal rate of tubular phosphate reabsorption divided by the glomerular filtration rate (Tm_p/GFR). For its clinical assessment either direct phosphate loading with simultaneous measurement of GFR is performed, or the nomogram described by Walton and Bijvoet is used. In order to test the validity of the two methods, we compared in 20 infants and 31 children the fasting values of phosphate reabsorption [endogenous phosphate reabsorption/inulin clearance (T_p/C_in) and T_p] with those obtained after phosphate loading [maximal phosphate reabsorption (Tm_p) and Tm_p/C_in], and both with those derived from the nomogram. In addition the fasting T_p/C_in of 50 infants and 143 children could be compared with the nomogram. The results demonstrate that the directly measured T_p/C_in was the same as the directly measured Tm_p/C_in and that the measured Tm_p/C_in was correctly estimated by the nomogram. However, the comparison of fasting T_p/C_in with nomogram-derived values showed a systematic error, by which the latter values were higher than those measured. The discrepancy was due to the splay of the phosphate titration curve, which was found by Bijvoet when the ratio of phosphate clearance (C_p) corrected for GFR (C_p/GFR) fell below 0.2. The incorporation of this splay in the nomogram could not be confirmed by data measured in our children. It is concluded that fasting T_p is already maximal and that, therefore, no phosphate loading is necessary to estimate Tm_p. Furthermore, there is no evidence of a major splay, which makes the nomogram incompatible below a C_p/GFR ratio of 0.2. For clinical assessment we recommend use of the formula Tm_p/GFR=P_p–(U_p×P_crea/U_crea) where P_p, U_p, P_crea and U_crea refer to the plasma and urinary concentration of phosphate and creatinine respectively. This formula can be applied easily without the need to collect timed urinary specimens and is independent of the phosphate load.     

Role of the urinary concentrating process in the renal effects of high protein intake

High protein diet is known to increase glomerular filtration rate (GFR) and induce kidney hypertrophy. The mechanisms underlying these changes are not understood. Since the mammalian kidney comprises different nephron segments located in well-delineated zones, it is conceivable that the hypertrophy does not affect all kidney zones and all nephron segments uniformly. The present experiments were designed to study the chronic effects of high or low isocaloric protein diets (HP = 32% or LP = 10% casein, respectively) on kidney function and morphology in Sprague-Dawley rats. HP diet induced significant increases in kidney mass, GFR, free water clearance, and maximum urine concentrating ability. Kidney hypertrophy was characterized by: 1. a preferential increase in thickness of the inner stripe of the outer medulla (IS) (+54%, P less than 0.001, while total kidney height, from cortex to papillary tip, increased only by 18%); 2. a marked hypertrophy of the thick ascending limbs (TAL) in the inner stripe (+40% epithelium volume/unit tubular length, P less than 0.05) but not in the outer stripe nor in the cortex; 3. an increase in heterogeneity of glomeruli between superficial (S) and deep (D) nephrons (D/S = 1.47 in HP vs. 1.17 in LP, P less than 0.05). In contrast, normal kidney growth with age and kidney hypertrophy induced by uninephrectomy were not accompanied by preferential enlargement of IS structures. The morphologic changes induced by high protein intake parallel those we previously reported in rats fed a normal diet (25% protein) but in which the operation of the urine concentrating mechanism was chronically stimulated by ADH infusion or by reduction in water intake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment and interpretation of the tubular threshold for phosphate in infants and children

Studies in the last decade demonstrated that in children tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) is identical to TP/GFR; TP indicating tubular phosphate reabsorption under basal conditions, without phosphate load. TP/GFR is calculated from the formula TP/GFR=S_P–U_P×S_CrU_Cr, based on simultaneous urine and blood creatinine and phosphate concentrations, and is applicable in both the fasting and non-fasting child. These studies also demonstrated that the use of Walton and Bijvoet nomogram in children may result in overestimation of TmP/GFR compared with TP/GFR calculated from the above formula. When using the formula, one should bear in mind that creatinine is used to express GFR and as a result a significant deviation from true GFR may occur in patients with renal failure. Therefore when employing TP/GFR for the investigation of the renal handling of phosphate in children, three factors should be taken into consideration: (1) the formula in reality expresses TP/C _Cr; (2) only data obtained by exactly the same methodology can be used as reference values; data obtained from studies in which the nomogram was utilized or in which methods other thanC _Cr were used to measure GFR should not be used for reference; (3) in patients with renal failure, TP/C _Cr will significantly overestimate TP/C _inulin.     

Renal functional reserve in transplanted and native single kidneys of children and adults

Renal functional reserve (RFR) after an oral protein load was evaluated in 36 cyclosporine-treated children following kidney transplantation (Tx), in 15 kidney donors (Don), and in 15 children with single kidneys (Nx/Ag). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by clearances of inulin (and creatinine) and para-aminohippurate during water diuresis. Baseline and stimulated GFR and ERPF were determined and RFR was calculated as the difference between stimulated and baseline values. Baseline GFR and ERPF in Tx were lower than in Don and Nx/Ag. Both GFR and ERPF increased significantly in all groups from baseline to stimulated values. RFR GFR was 23%±3%, 20%±3% and 15%±3% in Tx, Don, and Nx/Ag and RFR ERPF 35%±4% in Tx, which was significantly higher than 20%±4% and 15%±3% in the two other groups respectively. Stimulated GFR and ERPF in Tx correlated with kidney length. No differences were seen in recipient-donor pairs, except for higher fractional increases of ERPF in recipients. There was no correlation between RFR measured by clearance of creatinine and clearance of inulin. In conclusion, cyclosporine-treated children following renal Tx were found to have a renal reserve capacity. Received September 19, 1995; received in revised form September 16, 1996; accepted October 1, 1996     

Ethical Issues of Organ Transplantation in Chinese Community: Perspectives of Health Professionals, Legal Professionals, and Religious Experts in Taiwan and Mainland China

Objective

This study aimed to compare the perspectives of leading ethical issues related to organ transplantation as perceived by health professionals (HP), legal professionals (LP), and religious experts (RE) from Taiwan (TW) and Mainland China (MC).

Materials and Methods

A purposive sample including TW's organ transplant health professionals (OTHP), LP, and RE and MC's HP was obtained in this qualitative research. Data were analyzed by content analysis.

Results

A total of 127 subjects participated in this project (n = 119 in TW, 8 in MC). They were HP (n = 92), RE (n = 25 TW), and LP (n = 10 TW). Seven ethical dilemmas were reported: (1) difficulties in touching the hearts of the public (HP 100%, LP 100%, RE 100%); (2) challenges in helping donors and their families (HP 96%, RE 80%, LP 50%); (3) competence and availability of HP (HP 93%, RE 72%, LP 50%); (4) questionable social farewell (HP 92%, RE 20%, LP 100%); (5) questionable legitimacy of prisoners' motivations (LP 90%, RE 64%, HP 60%); (6) worry about public discrimination (LP 90%, HP 50%, RE 20%); and (7) challenges to families in taking care of the recipients (HP 87%, LP 70%, RE 52%).

Conclusions

To provide holistic care, HP need to invite RE to provide spiritual support for the donors of cadaveric organs, recipients, and their families. Reliable LP can help them to complete the sophisticated legal procedures. With help from this triangulated collaborative team, the value of organ transplantation will be appreciated by the public.     

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.     

Differentiation of pancreatic ductal carcinoma cells associated with selective expression of protein kinase C isoforms

Background: The signal transduction pathways important in regulating the growth and differentiation of malignant cells are poorly understood. Recent evidence has implicated activation of the protein kinase C (PKC) family of signaling proteins in pancreatic carcinoma during cytokine-induced cytostasis and differentiation. Methods: A human pancreatic adenocarcinoma (HPAC) cell line was exposed to tumor necrosis factor- (TNF-; 40 ng/ml) for 6 days. Cytostasis and viability were confirmed by daily MTT [(3(4,5)-dimethyl-thiazol-2-yl) 2,5-diphenyl-tetrazolium bromide] and trypan exclusion assay. Protein fractions were isolated daily and subjected to immunoblot analysis for the normal (terminally differentiated) pancreatic ductal cell marker carbonic anhydrase II (CA II) as well as specific PKC isoforms (, , , , and). Results: Growth arrest occurred in HPAC cells after exposure to TNF- for 48 h, with viability maintained above 90% throughout the 6-day time course. CA II immunoreactivity was not detected in untreated controls but appeared after 2 days of TNF- exposure, peaking on day 6. Concurrently, TNF- induced the selective downregulation of PKC-, whereas PKC- levels increased. PKC- and PKC- immunoreactivity did not change. The atypical PKC- isoform developed a doublet banding pattern in response to TNF-, although overall PKC- levels did not change. Conclusions: TNF--induced growth arrest and differentiation in HPAC cells is associated with the selective downregulation of PKC- and upregulation of PKC-.Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Renal function following unilateral nephrectomy for neuroblastoma and Wilms' tumour

To estimate the side effects of chemotherapy and the influence of age at the time of nephrectomy on renal function, we investigated renal function in 34 uninephrectomised children with neuroblastoma (NB) or Wilms' tumour (WT). The results were compared with 6 controls who underwent nephrectomy for non-malignant disease. Study of renal function was primarily based on the clearance of inulin and para-aminohippuric acid (C _in andC _PAH, ml/min per 1.73 m²). No significant differences inC _in/C _PAH (mean±SD) were found between the NB group (90±24/421±95), WT group (85±17/386±104) and the controls (93±13/430±61). Children with NB and WT were divided into two subgroups according to the theoretical nephrotoxic risk. There was no significant difference in renal function between NB or between WT subgroups. Cumulative cisplain doses in children with NB did not affect renal function significantly. The age at time of unilateral nephrectomy (2 years vs. 2 years) was not associated with a higher risk of renal damage in WT children, whereas in NB children the filtration fraction (C _in:C _PAH) was higher in younger children (mean±SD: 0.243±0.023 vs. 0.191±0.041). In conclusion, uninephrectomised children with NB are supposed to have a higher risk of drug-induced renal impairment compared with those with WT. Our data do not confirm this hypothesis, since renal function was comparable to controls in both groups, except in younger patients with NB who show a high filtration fraction. Since the survival of children with NB has improved, a longer follow-up of their renal function in needed.     

Optimising nutrition in chronic renal insufficiency—progression of disease

There is a lack of evidence to support the belief that dietary measures are beneficial in slowing the progression of chronic renal insufficiency (CRI). We prospectively monitored nutrient intakes and progression of CRI over a 2-year period in children aged 2–16 years with differing levels of severity of CRI, as part of their ongoing joint medical/dietetic care. Children were grouped following [⁵¹Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min per 1.73 m²) estimations, into normal kidney function [GFR >75, mean 106 (SD 19.5), n =58], providing baseline data only, mild (GFR 51–75, n =25), moderate (GFR 25–50, n =21), and severe (GFR <25, n =19) CRI. Children with CRI were followed for 2 years, with 51 completing the study (19 mild, 19 moderate, 13 severe CRI) and were excluded if they subsequently required dialysis. Regular medical and dietary advice was provided and yearly 3-day semi-quantitative dietary diaries and baseline and 6-monthly measurements of blood pressure and urinary protein/creatinine ratio were obtained. Mean reductions in estimated GFR over 2 years were –9.4, –5.8, and –6.0 ml/min per 1.73 m² for mild, moderate, and severe CRI, respectively. Mean systolic blood pressure standard deviation score (SDS) fell significantly in all groups by 0.7 SDS, whereas there was little change in proteinuria. From reported dietary intakes, median sodium intakes increased (+10 mmol/day) and protein intakes decreased (–0.4 g/kg per day). Median phosphate intakes did not change significantly, whereas calcium intakes fell in all groups, with an overall median of –20% reference nutrient intake (RNI) (F =33.3, P <0.001). Of children with moderate CRI, 65% finished with calcium intakes below 80% RNI, and parathyroid hormone (PTH) concentrations significantly increased in this group (F =6.0, P =0.021). Higher phosphate and sodium intakes were associated with greater deterioration in estimated GFR in children with mild CRI (r ²=0.30, P =0.02; r ²=0.31, P =0.02, respectively). There was no such correlation for protein intake or PTH. This study emphasises the need for a joint medical and dietetic approach and indicates a number of interventions other than protein restriction, which could be commenced early in children with CRI in an attempt to delay progression.     

Creatinine for estimation of glomerular filtration rate

The aim of this study was to evaluate the plasma creatinine concentration (P_Cr) and creatinine clearance (C _Cr) for estimation of glomerular filtration rate (GFR). Inulin clearance (C _in) was used as the reference standard for GFR. Thirty-nine concurrentC _in andC _Cr studies provided data for comparingC _in with the measuredC _Cr and with the calculatedC _Cr (calc-C _Cr). (Calc-C _Cr=k·L/P_Cr, where L=height in centimeters and k is the proportionality constant.) Thirty-one children 5.3–20.8 years of age, withC _in ranging from 2.8 to 138.8 ml/min per 1.73 m², participated in these studies at The Children's Mercy Hosptial. The measuredC _Cr was 16.7±10.3 ml/min per 1.73 m² (P<0.001) greater than theC _in, and the calc-C _Cr overestimatedC _in by a mean of 31.6±20.8 ml/min per 1.73 m² (P<0.001). Although there is good correlation betweenC _in andC _Cr (r=0.96), andC _in and calc-C _Cr (r=0.90), the 95% confidence intervals are quite broad. Hence, theC _Cr and the calc-C _Cr, derived using Schwartz values for k, consistently overestimate GFR. However, if the k value in the equation GFR=k·L/P_Cr is derived from k=C _in/L, rather than from k=C _Cr·P_Cr/L, a more accurate estimate of GFR may be obtained.     

Single-Center Long-Term Follow-Up of Kidney Donors in Argentina (Hospital Italiano de Buenos Aires)

Introduction

Living kidney donor (LKD) transplantation is increasing due to organ shortage. Clinical studies have shown that the risk of developing end-stage renal disease (ESRD) in donors is similar to that in the general population. Our goal was to evaluate postdonation renal outcomes assessed by glomerular filtration rate (GFR), proteinuria, and blood pressure.

Effects of age at the time of unilateral nephrectomy and dietary protein on long-term renal function in rats

Glomerular filtration rate (GFR) and urinary protein excretion (UpV) were studied in male rats with a uninephrectomy at 3 (UNX-3) or 15 weeks of age (UNX-15) and fed a low (12%, LP), normal (24%, NP) or high (36%, HP) protein diet. Measurements were made every 12 weeks throughout the entire life-span. The UNX rats were compared with sham-operated (2K) rats of the same age and on the same diets. At 12 weeks after surgery, the GFR of UNX rats, corrected for differences in body weight, age and protein intake (GFRcor), ranged between 73% and 77% of that of 2K rats. On the HP and NP diet, UpV was higher in UNX-3 than in UNX-15 rats. On the LP diet, UpV was equally low in both groups. Long-term follow-up indicated that the GFR of UNX rats on the HP diet started to decline first, followed by those on an NP diet, while those on an LP diet had the longest period of stable GFR. For UNX rats, the time to reach a GFRcor of 50% was used as an indicator of the length of renal survival. Analysis of variance of the renal survival times indicated a highly significant interaction between the protein diet and age at the time of UNX. On the HP diet, UNX-3 rats have a shorter renal survival time than UNX-15, while on the LP diet UNX-3 rats have a longer renal survival time. This indicates that the long-term outcome of UNX at young age depends on the protein intake. Simultaneous stimulation of renal growth by HP intake and compensatory growth, during the period of normal kidney growth, results in early damage of the remaining kidney.     

Renal adaptation to phosphate deprivation: lessons from the X-linkedHyp mouse

The X-linkedHyp mutation, a murine homologue of X-linked hypophosphatemia in humans, is characterized by renal defects in phosphate reabsorption and vitamin D metabolism. In addition, the renal adaptive response to phosphate deprivation in mutantHyp mice differs from that of normal littermates. WhileHyp mice fed a low phosphate diet retain the capacity to exhibit a significant increase in renal brush-border membrane sodiumphosphate cotransport in vitro, the mutants fail to show an adaptive increase in maximal tubular reabsorption of phosphate per volume of glomerular filtrate (TmP/GFR) in vivo. Moreover, unlike their normal counterparts,Hyp mice respond to phosphate restriction with a fall in the serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)₂D] that can be ascribed to increased renal 1,25(OH)₂D catabolism. The dissociation between the adaptive brush-border membrane phosphate transport response and the TmP/GFR and vitamin D responses observed inHyp mice is also apparent in X-linkedGy mice and hypophysectomized rats. Based on these findings and the notion that transport across the brush-border membrane reflects proximal tubular function, we suggest that the adaptive TmP/GFR response requires the participation of 1,25(OH)₂D or a related metabolite and that a more distal segment of the nephron is the likely target for the 1,25(OH)₂D-dependent increase in overall tubular phosphate conservation.     

Comparison of two formulae for estimation of glomerular filtration rate in children

Glomerular filtration rate (GFR) was measured in 216 studies in 151 children using the cimetidine protocol. This was compared with the GFR calculated using Légers pharmacokinetic equation and with that calculated using k*L/[Cr]_s (constant × length in centimeters divided by serum creatinine concentration). The GFR calculated using the equation GFR=k*L/[Cr]_s yielded a closer approximation to the measured GFR than that using Légers pharmacokinetic equation. Currently there is focus on screening children for decreased GFR to identify those with asymptomatic chronic kidney disease at a time when intervention may delay progression to chronic renal failure. This study showed close approximation of the calculated GFR with the measured GFR using the equation GFR=k*L/[Cr]_s, when the values for k were determined in the laboratory in which creatinine was measured.     

Effects of Phosphonoformic Acid and Renagel on Renal Type IIa Sodium-Dependent Phosphate Cotransporter mRNA Expression in Hyperphosphatemia Rats

Objective: To investigate the effects of phosphonoformic acid (PFA) and sevelamer hydrochloride (Renagel) on renal type IIa sodium-dependent phosphate cotransporter (NaPi-2) mRNA expression in hyperphosphatemia rats. Methods: Thirty rats were randomly divided into five groups based on the diet for 2 weeks after 5/6 nephrectomy (Nx): Nx + high-phosphate (HP; 1.2% P) diet; Nx + low-phosphate (LP; 0.2% P) diet; HP + PFA (injected with 0.15 g/kg PFA daily); HP + Saline (injected with the same amount of saline daily); and HP + Renagel (2%) group. Another 12 rats were sham operated and divided into Sham + HP and Sham + LP groups. Serum ionized calcium, phosphorus (P), and intact parathyroid hormone (iPTH) were measured on days 2, 7, and 14. Serum 1,25(OH)₂D₃ was measured on day 14 and NaPi-2 mRNA levels were assayed by RT-PCR. Results: PFA decreased iPTH level but had no effect on NaPi-2 mRNA expression. Renagel decreased serum P and iPTH levels, but upregulated renal NaPi-2 mRNA expression. Conclusions: Both PFA and Renagel are effective drugs to decrease iPTH level and they might be potential candidates for treatment of clinical secondary hyperparathyroidism. Renagel can also decrease serum P and upregulate renal NaPi-2 mRNA expression.     

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 hypoplasia: lessons from Pax2

The functions of Pax2 during renal development are many. It organizes caudal descent of the nephric duct, emergence of the ureteric bud, branching morphogenesis, and sustained arborization of the collecting system. In this review, we use lessons from the study of Pax2 as organizing principles to focus on the developmental processes which, if disrupted, might lead to renal hypoplasia in humans. We consider the problem of renal hypoplasia as a continuum, ranging from renal agenesis to subtle congenital nephron deficits. Early failure in the first two developmental stages (e.g. homozygous inactivation of Pax2) should preclude formation of metanephric kidneys and cause bilateral renal agenesis, incompatible with life. Interference with the later stages affects the extent of branching morphogenesis (e.g. heterozygous Pax2 mutations). Although the resulting nephron deficits are compatible with life, they may be moderately severe and account for up to 40% of the children in dialysis and transplant units around the world. Finally, the effect of Pax2 on apoptosis in the branching ureteric bud seems to imply a quantitative process which is finely tuned. Modest changes in this program could account for subtle nephron deficits in normal humans and increased risk of hypertension or susceptibility to acquired renal disease later in life.     

Development of injury in a rat model of chronic renal allograft rejection: effect of dietary protein restriction

Non-allogeneic factors such as increased nephron “workload” may contribute to chronic renal allograft rejection. Reducing dietary protein from 20 % to 8 % was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient, “tolerised” by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low-protein (LP) group 1 month after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF-β ₁ mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8 % lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage. Received: 17 June 1998 Accepted: 23 September 1998