Brenda Montane

Renal Disease in Children with the Acquired Immunodeficiency Syndrome

Abstract Of 155 children with the acquired immunodeficiency syndrome (AIDS) whom we evaluated during a 6 1/2-year period, 12 were found to have proteinuria. Histologic studies of tissue from these 12 patients revealed a wide spectrum of renal disease: focal glomerulosclerosis in 5, mesangial hyperplasia in 5, segmental necrotizing glomerulonephritis in 1, and minimal change disease in 1. In addition, 6 had tubulointerstitial infiltrates, and 10 had glomerular dense deposits. All 10 renal specimens studied by electron microscopy contained endothelial tubuloreticular inclusions. The mean age (±SD) of the five patients with focal glomerulosclerosis when this condition was identified was 27±19 months. All five had severe renal failure within a year and died of other causes during the following year. The mean age of the five patients with mesangial hyperplasia was 38±31 months. Although none of them went on to have renal failure, four died within 8±7 months. Ten of the 12 patients with proteinuria died during ...

Early blood transfusions protect against microalbuminuria in children with sickle cell disease

Microalbuminuria (MA) is an early indicator for glomerulopathy in sickle cell disease (SCD).

Profiling proteinuria in pediatric patients.

This study was designed to characterize proteinuria in children with kidney disease. Random urine samples from 250 pediatric patients were examined by quantitative measures of total protein (pr), albumin (Alb), and creatinine (cr). Patient diagnoses were subjectively categorized as “Glomerular” (GD) or “Tubulo-interstitial” disease (TD) in origin. Proteinuria was quantitated by the random urine protein-to-creatinine (Upr/cr) ratio, and glomerular proteinuria was assessed as the albumin-to-creatinine ratio (Ualb/cr) and percentage albuminuria (%Alb=Alb/pr*100). The non-albumin fraction (1−Alb/pr) includes low-molecular-weight proteins and micro- and macroglobulins. Of the 250 patients, 112 (45%) had GD and 138 (55%) had TD. Both proteinuria and albuminuria correlated with a decline in glomerular filtration rate (GFR) (r=−0.4; p<0.0001). Those with GD averaged significantly greater %Alb than those with TD at all levels of proteinuria (p<0.0001). With loss in GFR, %Alb increased significantly in patients with TD (18±13 to 47±30%; p<0.001) and GD (56±26 to 74±15%; p<0.01), respectively. The %Alb at all levels of GFR averaged <50% in those with TD and >50% in those with GD. In conclusion, random Ualb/cr, Upr/cr, and %Alb provide a simple and inexpensive assessment of proteinuria and may profile renal disease activity and response to therapy in pediatric patients.

Human immunodeficiency virus nephropathy

Varying components of the syndrome of human immunodeficiency virus nephropathy (HIVN) have been described, the most pertinent including proteinuria/nephrotic syndrome, progressive azotemia, normal blood pressure, enlarged and hyperechoic kidneys, rapid progression to end-stage renal disease (ESRD), and no response to treatment regimens. The diagnosis of HIVN requires identification of excessive proteinuria or albuminuria, determined by a total protein excretion on a timed urine collection or a high protein/creatinine ratio in a random specimen. Various pathological lesions have been found in HIVN. The lesion of focal and segmental sclerosis (FS/FSS) is most characteristic in adults and usually is associated with a rapid demise. FS/FSS also has been described in approximately one-half of the pediatric patients reported in the literature (31/64). Despite progression to ESRD, the clinical course in children with HIVN is less fulminant than in adults. Other reported histological findings include primarily mesangial hyperplasia as well as minimal change, focal necrotizing glomerulonephritis or lupus nephritis, and hemolytic uremic syndrome. In addition to glomerular pathology, interstitial findings of dilated tubules filled with a unique proteinaceous material, atrophied tubular epithelium, and interstitial cell infiltration are very common. On electron microscopy, most investigators have found tubuloreticular inclusion bodies in endothelial cells of glomerular capillaries. Treatment of patients who develop ESRD remains highly controversial. Most adult patients treated with hemodialysis have succumbed rapidly; peritoneal dialysis has been better tolerated. Transplantation in patients with HIV infection must be considered to be tentative, with reports of acceleration towards full blown acquired immunodeficiency syndrome in some and uneventful 5-year survival in others. The situation of the pediatric patient with HIVN remains unclear and awaits the benefit of experience.

ACE inhibition scintigraphy in the management of hypertension in children

Abstract Angiotensin converting enzyme (ACE) inhibition scintirenography was performed to help establish the diagnosis and plan treatment of renovascular hypertension (RVH) in 57 hypertensive pediatric patients, 33 infants and 24 children older than 1 year. In 16 of 33 hypertensive infants, ACE inhibition scintirenography established the diagnosis of RVH from renal ischemia (due to aortic or renal arterial thrombi). Two scintigraphic criteria were used for the diagnosis of RVH: criterion I, ischemic and damaged kidney (a non-functioning kidney on or off ACE inhibition) and criterion II, ischemic but not damaged kidney (ACE inhibition induced deterioration of function of the kidney). When criterion I was present and the contralateral kidney was normal, ACE inhibitors could be used for treatment of hypertension without deterioration of renal function; kidneys satisfying criterion I eventually involuted or manifested growth arrest and frequently caused persistent RVH, even after resolution of the thrombus, requiring nephrectomy. When criterion II was present bilaterally, or it was associated with criterion I contralaterally, the use of antihypertensive drugs other than ACE inhibitors was necessary in order to prevent renal insufficiency or failure from ACE inhibitors. However, kidneys with criterion II showed normal growth and, following retraction or dissolution of the aortic thrombus, hypertension resolved. In 2 of 24 hypertensive children older than 1 year, the test was diagnostic of branch renal artery stenosis; RVH was cured by selective angioplasty. ACE inhibition scintirenography is useful in the evaluation and planning of treatment in children with hypertension and may predict the outcome of therapy and ultimate renal function.

Role of Routine Urinalysis in Asymptomatic Pediatric Patients

This study was done to evaluate the spectrum of diagnoses and identify risk factors for significant kidney disease in asymptomatic children with proteinuria and/or microhematuria detected by routine urinalysis. Clinical and laboratory data were obtained by retrospective chart review of 239 patients referred to a tertiary care center. The predominant diagnosis in children with isolated microhematuria was hypercalciuria and with isolated proteinuria, orthostatic proteinuria. When microhematuria and proteinuria were present in combination, kidney disease was the predominant diagnosis. Urinalysis is a valuable tool to identify patients with kidney disease. The combination of microhematuria and proteinuria increases the risk of having significant kidney disease.

URINARY AND RENAL HISTOLOGICAL CHANGES IN CHILDREN WITH IMMUNODEFICIENCY SYNDROME (AIDS)

Patients with AIDS frequently develop circulating immune complexes (CIC) and elevated serum immunoglobulins which might predispose to renal disease. The latter has been recently described in >10% of adults with AIDS, but no such association has been reported in children. We studied 15 patients ([xmacr ] age 11 months, range 2-24) with proven AIDS (defined by an inverted T4/T8 ratio plus Kaposis Sarcoma or unusual infections). All evidenced intermittent proteinuria (up to 55 mg/kg/day) and 7 had hematuria (up to 50 RBCs/HPF) and/or casts. Serum creatinine was normal ([xmacr ] 0.6 mg/dl). Elevated ESR (max. 116 mm/hr) was noted in all patients, increased CIC (ClQ and Raji) in 6 and high serum IgG (max. 4,910 mg/dl) in 10. Serum C3 and C4 were normal in all. Renal autopsy material was available in 7 patients of which 3 had abnormal findings: 1 with markedly increased mesangial matrix and nuclei, 1 with profuse electron-dense deposits in the mesangium, and 1 with immunofluorescent deposits of IgM and C3 in the mesangium. We conclude that AIDS is often associated with urinary and renal histological changes. These changes are not as severe as those in adults possibly due to the shorter duration of the disease, lack of associated complicating factors (drug addiction, etc.,) or to the renal and immune characteristics of children ; still they may carry prognostic significance.

Erratum: Serum cystatin C levels in children with sickle cell disease (Pediatric Nephrology (2006) vol. 21 (533-537) 10.1007/s00467-006-0033-6)

In the introduction, the expanded form of CSSCD should read Cooperative Study of Sickle Cell Disease (CSSCD) and not Comprehensive Study of Sickle Cell Disease.

Is Ethnicity an Important Prognostic Indicator in the Development and Progression of HIV Nephropathy in Children? 1839

A cohort of 263 children with perinatally transmitted HIV infection was followed prospectively at the University of Miami/Jackson Childrens Hospital for the development of overt HIV infection and associated nephropathy (HIVN). Definitive HIV infection was confirmed by persistent titers of HIV antibodies and/or positive viral PCR assays after 18 months. Nephropathy was defined in patients determined to have persistent proteinuria greater than or equal to 1+ on urinary Dipstick(R) in the absence of fever on consecutive urines at least 2 weeks apart. Quantitation of proteinuria was performed by timed collections(UprV) or urine protein: creatinine ratios (Upr/Ucr). Significant proteinuria was defined as a UprV≥0.1 gram/m2/day or Upr/Ucr≥0.2. Nephrotic proteinuria was defined as UprV≥1 gram/m2/day or Upr/Ucr≥2. The racial and ethnic demographics of the population were predominantly Black(74%) with the remainder Hispanic (14%) and Caucasian (12%). 72 of the 263 children developed active HIV infection. Of these, 44 had persistent proteinuria making the actual incidence of HIVN as high as 54%. Twelve of the 44 (16.7%) had nephrotic range proteinuria. The overall mortality for the HIV+ children not attributable to renal disease has been 50% over 5 years. Only 6(13.6%) have progressed to end stage renal disease (ESRD) requiring dialysis. All were of African-American or Haitian descent. The renal pathology in all ESRD patients was focal glomerulosclerosis with nephrotic range proteinuria preceding the deterioration to ESRD. The mortality of the HIV+ dialysis patients was not different from the rest of the HIV+ children in the study. These data suggest a strong influence of race and ethnicity in the development and progression of HIVN in the pediatric population.

Highlights of Major Differences Between Children and Adults with HIV-Associated Nephropathy

Major differences between human immunodeficiency virus (HIV) associated nephropathy (HIVN) in children and HIVN in adults include the following: HIVN occurs in both HIV-1 + and AIDS adults, but apparently only in AIDS children. In HIVN patients, the virus has been transmitted to adult males mostly by intravenous drug use, and to adult females mostly by intercourse with infected males, but the virus has been transmitted to male and female infants and children by the mother. Renal histology changes in HIVN adults are mostly of the focal and segmental sclerosis (FSS) type, but FSS type changes are found in only one-third-one-half of HIVN children. The onset of chronic renal failure in adults heralds a rapid (few weeks) course to death, but in children the course is much slower (several months). Acute renal failure is rarely diagnosed in HIVN children while it is commonly diagnosed in HIVN adults.