Modulating the progression in IgA nephropathy.

IgA nephropathy affects almost 1% of the population and yet the diagnosis is often missed. This significant kidney disease is often progressive with 25% of the patients going on to end-stage kidney disease over the course of 25 years. This minireview describes the clinical presentations in children and young adults. Therapeutic options are discussed including angiotensin-converting enzyme blockade, steroids, cytotoxics, tonsillectomy, fish oil, vitamin E, singly or in combination, in order to modulate the rate of progression.

Effect of the GH secretagogue L-163,255 and restricted feeding time on GH pulsatility in the rat.

OBJECTIVE: To determine the effect of repeated treatments with the growth hormone secretagogue (GHS) L-163,255 on the pulsatile release of GH when administered in meal-fed rats before and after feeding. DESIGN: The first group of rats (AL, n=6) had food available ad libitum. The second (restricted, R, n=6), third (GHSB, n=6), and fourth (GHSA, n=6) groups were fed from 1100 to 1400 h. Groups GHSB and GHSA were given GHS by gavage, 3.0 mg/kg L-163,255, at 1000 h (before feeding, B) and at 1500 h (after feeding, A) respectively. Three weeks after the initiation of the treatment, blood samples were collected at 10-min intervals over 6 h, and GH levels were determined. RESULTS: In group R, the concentrations of GH were higher before feeding (17.6+/-2.4 ng/ml) than during feeding (11.2+/-1.2 ng/ml), P<0.05. The average concentrations of the peak in response to GHS were higher when GHS was administered before (121.70+/-33.68 ng/ml) than after (49.67+/-17.87 ng/ml) feeding. The mass of GH, as calculated by deconvolution analysis was also higher in the GHSB group than in the GHSA group (251.6+/-64.1 ng/ml per min vs 85.3+/-22.9 ng/ml per min respectively, P<0.05). CONCLUSION: L-163,255 is effective in inducing GH release after repeated oral administration in rats. The effectiveness is greater when GHS is administered before rather than after feeding in meal-fed animals.

Acute kidney failure: a pediatric experience over 20 years.

BACKGROUND: Acute kidney failure in children is a catastrophic, life-threatening event. OBJECTIVE: To compare and contrast 2 decades of data, analyzing the underlying causes, associated multiple organ system failures, outcome of dialysis procedures, and other variables of interest. DESIGN: Retrospective examination of clinical data collected between January 1, 1979, and December 31, 1998. SETTING: Regional health care center in the mid-Atlantic area. PARTICIPANTS: Two hundred twenty-eight patients, aged from 1 day to 18 years, had acute kidney failure and were referred to a pediatric nephrology service. MAIN OUTCOME MEASURES: Characteristics, percentage of mortality, intensive care unit admission, procedures, and other variables and causes of acute renal failure. RESULTS: The total number of cases analyzed represented 7% of all patients presented to the pediatric nephrology service. Sex distribution, ethnicity, and survival statistics were unchanged between both decades. The overall survival rate was 73%. One hundred fifty-four patients (68%) were admitted to the pediatric intensive care unit. The following 106 acute extracorporeal procedures were performed on 93 patients (41%): 12 patients received extracorporeal membrane oxygenation, 52 patients underwent peritoneal dialysis, 32 underwent hemodialysis, 3 patients received continuous venovenous hemofiltration, and 7 patients received continuous arteriovenous hemofiltration. Sepsis and burns, other leading causes of acute renal failure in the first decade, are replaced in the second decade by hematologic-oncologic complications and pulmonary failure. CONCLUSIONS: Acute kidney failure following repair of cardiac lesions remains unchanged as a leading risk factor of mortality in both decades. Three organ system failures were associated with more than a 50% mortality rate. Predialysis low serum albumin concentrations emerged as a significant copredictor of mortality.

Evaluation of the hypertensive infant: a rational approach to diagnosis.

This article reviews the literature and describes a methodologic approach to the diagnosis of hypertension in the young infant. The numerous etiologies of hypertension have been discussed and normative blood pressure data for neonates and infants have been provided. Techniques for accurate blood pressure measurement in the intensive care setting and for routine outpatient settings, are discussed. The lengthy discussion of radiologic approach to imaging can be summarized with the following suggested algorithm. Initial screening should be performed with gray-scale sonography, to identify renal parenchymal or collecting system abnormalities, including mass lesions and congenital anomalies. Further imaging with color and duplex Doppler sonography detects renal arterial or aortic thrombosis, and alterations in the arterial waveform caused by intrinsic or extrinsic renal artery narrowing. The major limitation of Doppler sonography is the recognition that disease in accessory renal arteries or in small segmental intrarenal arteries may frequently be undetected. Functional imaging with ACEI renography should follow renal sonography to detect hemodynamically significant renovascular disease (with a sensitivity and specificity of approximately 90%); intravenous enalaprilat is the preferred ACEI. Angiography should be reserved for older children in whom interventional percutaneous angioplasty may be more feasible. A young infant with hypertension caused by renal artery stenosis should be controlled medically until he or she is large enough to undergo angiography and angioplasty successfully. CT angiography and MR angiography, although promising in the adult population, may not adequately resolve the small intrarenal vessels, which are frequently the culprit in renovascular hypertension of infancy.

Effects of deflazacort and cortisone on cellular proliferation in the rat thymus.

Deflazacort is a relatively new glucocorticoid with significant immunosuppressant activity and presumably fewer side effects. The present study was designed to compare the effects of deflazacort on the proliferative activity of thymus cells and thymolysis with the growth inhibition. We treated Long-Evans rats for nine days with cortisone (CORT, 5.0 mg/day), deflazacort (DFZ, 0.15 mg/day), and control vehicle (CTRL). Animals were sacrificed 1 hour after injection of bromodeoxyuridine (BrdUrd) on day 10. BrdUrd-labeled thymic cells were quantified without knowledge of treatment. A Labeling Index (LI), expressed as the number of BrdUrd BrdUrd-labeled cells per 100 total cells and the Numerical Density (ND), expressed as the total number of cells per 100 microm(2) were calculated. Treatment with either glucocorticoid resulted in a significant and equal decrease of thymus weight, indicating a marked reduction in total immunogenic tissue. A general alteration of thymic histological structure occurred in the CORT group. The LI was not different between CTRL and DFZ groups, 6.9 and 7.9% of cells were labeled respectively. In the CORT group, the LI was 2.5%. With respect to Numerical Density, the CTRL group had the greatest value (14.6 +/- 0.4 cells/100 microm(2)), with the DFZ (12.3 +/- 0.06 cells/100 microm(2)) and CORT groups being significantly lower (10.4 +/- 0.5 cells/100 microm(2)). Although regression analysis of thymus weight pointed to bioequivalence of the glucocorticoid dosages used, BrdUrd-labeling raised the possibility that the cells still present in the thymus of DFZ-treated animals retained, at least partially, their normal capacities for proliferation.

Obstructive uropathy: an important cause of chronic renal failure in children.

Care of individuals with renal failure continues to impose a tremendous burden on our national health care budget. Chronic renal failure is the final common denominator of a multiplicity of pathologic processes, some of which progress silently over years. Of these, obstructive uropathy is a prominent cause of kidney failure, accounting for 16.5% of all pediatric renal transplants in 1997. The pathophysiology of obstructive uropathy is reviewed as the basis for a differential diagnosis. In view of the significant role played by obstructive uropathy in the development of renal failure, early and definitive treatment of this clinical entity is imperative.

Understanding Bartter syndrome and Gitelman syndrome.

BACKGROUND: We aim to review the clinical features of two renal tubular disorders characterized by sodium and potassium wasting: Bartter syndrome and Gitelman syndrome. DATA SOURCES: Selected key references concerning these syndromes were analyzed, together with a PubMed search of the literature from 2000 to 2011. RESULTS: The clinical features common to both conditions and those which are distinct to each syndrome were presented. The new findings on the genetics of the five types of Bartter syndrome and the discrete mutations in Gitelman syndrome were reviewed, together with the diagnostic workup and treatment for each condition. CONCLUSIONS: Patients with Bartter syndrome types 1, 2 and 4 present at a younger age than classic Bartter syndrome type 3. They present with symptoms, often quite severe in the neonatal period. Patients with classic Bartter syndrome type 3 present later in life and may be sporadically asymptomatic or mildly symptomatic. The severe, steady-state hypokalemia in Bartter syndrome and Gitelman syndrome may abruptly become life-threatening under certain aggravating conditions. Clinicians need to be cognizant of such renal tubular disorders, and promptly treat at-risk patients.

Risk profiles of progression in primary focal segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a component of childhood nephrotic syndrome occurring in 10%-20% of all cases. Over time, 25%-50% of children with FSGS develop kidney failure disease. We followed a cohort of children with FSGS in order to delineate the risk profile of progression to kidney failure (KF). METHODS: We evaluated patient data collected from 1977 to 2002 at a regional mid-Atlantic nephrology center in the United States. KF was defined primarily for those patients whose serum creatinine (SCr) value doubled compared with the SCr value from a previous visit. Patients who received dialysis or a kidney transplant were also defined as having KF. We analyzed patient data for those who had at least two visits with SCr values recorded. Various baseline characteristics of patients who had developed KF and those with no kidney failure (NKF) were compared. Hazard ratios and correlation were used to further investigate potential risk factors of the kidney failure. We also compared the inverse SCr trend for KF and NKF patients using weighted linear regression. RESULTS: Thirty-four of 43 FSGS patients had adequate follow-up data. About 60% of the patients developed KF over the study period. The average age of the KF patients at diagnosis of FSGS was 9 years, and that of NKF patients 12 years (P=0.05). FSGS patients with KF had a significantly higher mean diastolic blood pressure (DBP) at baseline, compared to those with NKF (P<0.0001). Other baseline characteristics including race, body mass index (BMI), systolic blood pressure, total cholesterol, urinary protein/creatinine ratio and calculated glomerular filtration rate (cGFR) were not significantly different. Baseline DBP was a significant risk factor in progression to KF (HR: 1.03; 95%CI: 1.01-1.06). Inverse SCr values were significantly decreased over time in KF patients (P=0.01). CONCLUSIONS: The data of this study indicate that children diagnosed with FSGS who are younger than 10 years and have elevated baseline DBP are more likely to develop kidney failure. The non-significant hazard ratios for other baseline characteristics including gender, race, and BMI are not instrumental risk factors. These results may help understand what may affect progression towards kidney failure in children with FSGS.

Vitamin E in renal therapeutic regiments.

Administration of vitamin E in children with immunoglobulin A (IgA) nephropathy, focal segmental glomerulosclerosis (FSGS) and type I diabetes demonstrated potential towards ameliorating progression. Oral vitamin E therapy reduced endothelial dysfunction, lipid peroxidation and oxidative stress in patients with chronic kidney failure (CKF). Moreover, the use of vitamin E-bonded hemodialyzers reduced atherosclerotic changes, erythropoietin dosage and muscular cramps in patients on hemodialysis (HD). However, several controlled clinical trials failed to document beneficial effects on the study subjects' cardiovascular and renal outcomes. A recent report of increased all-cause mortality in adult patients receiving high dose vitamin E therapy has caused considerable concern and debate. These issues regarding the efficacy and safety of vitamin E in renal therapeutic regimens will be reviewed in this article.

Growth hormone and growth hormone-related mRNA in uremic rats: effect of a growth hormone secretagogue.

In experimental animals, the decreased growth during mild uremia is not accompanied by a loss in the capacity of the pituitary gland to secrete growth hormone (GH). With the development of orally administered GH "secretagogues" (GHS), it might be possible to stimulate growth during uremia without injections. This study was designed to determine the effects of the GHS, L-163,255. Uremia was induced by 5/6 nephrectomy (NX). GHS was given orally, 3 mg/kg, twice a week. Four groups of animals included: (1) sham-operated, (2) sham-operated, pair-fed, (3) uremic (NX), and (4) uremic, GHS-treated (NX+GHS). Blood sampling was conducted via intra-atrial catheters, and GH was quantitated. Pituitary GH mRNA was measured by Northern blot, and liver GH receptor and insulin-like growth factor-I mRNAs by RNAase protection. Untreated NX animals had a specific decrease in the "mass" of the GH pulses. A burst of GH was induced by GHS, but the pulsatile pattern of GH secretion over 6 h was not affected. An increase or a return to non-uremic levels of GH-related mRNAs occurred after GHS. Thus, GHS stimulated an acute burst of GH secretion and increased specific mRNAs encoding GH-related proteins in uremic animals.

Vitamin E therapy in IgA nephropathy: a double-blind, placebo-controlled study.

IgA nephropathy is the world's most common primary glomerulonephropathy. Recent evidence in a rat model implicated excessive production of oxygen-free radicals in the pathogenesis and suggested that vitamin E-treatment ameliorated progression. We studied this antioxidant therapy on the glomerular filtration rate (GFR), proteinuria and hematuria in biopsy-proven IgA nephropathy in children. The duration of treatment or placebo was 2 years, with vitamin E treatment consisting of 400 IU/day in children weighing <30 kg, and twice that dose for those >30 kg. We measured GFR at entry, midpoint and exit. At baseline and at 4-month intervals after randomization, urinary protein/creatinine ratios and urinalysis were examined. The mixed model procedure with log transformation was used in data analysis to test treatment difference as well as the potential time effect. Fifty-five patients were randomized and 38 completed at least 1 year of follow-up. At entry, the clinical characteristics were not different between the treatment and placebo groups. There was a trend toward better preservation of GFR in vitamin E-treated versus placebo patients, 127+/-50 vs. 112+/-31 ml/min/1.73 m(2), respectively ( P=0.09). The urinary protein/creatinine ratio was significantly lower in the vitamin E-treated group vs. placebo; 0.24+/-0.38 vs. 0.61+/-1.37 ( P<0.013). However, there was no difference in the prevalence of hematuria between the groups. Vitamin E treatment in our study patients was associated with significantly lower proteinuria, but no effect on hematuria. While there was a trend toward stabilization of GFR in the vitamin E-treated patients, long-term treatment and follow-up are needed to determine whether antioxidant therapy is associated with preservation of renal function in IgA nephropathy.