treatment algorithm for children with lupus nephritis to prevent developing renal failure

Chronic kidney disease is one of the most common complication of systemic lupus erythematosus, which if untreated can lead to the end-stage renal disease [ESRD]. Early diagnosis and adequate treatment of lupus nephritis [LN] is critical to prevent the chronic kidney disease incidence and to reduce the development of ESRD. The treatment of LN has changed significantly over the past decade. In patients with active proliferative LN [Classes III and IV] intravenous methylprednisolone 1 g/m[2]/day for 1-3 days then prednisone 0.5-1.0 mg/kg/day, tapered to <0.5 mg/kg/day after 10-12 weeks of treatment plus mycophenolate mofetile [MMF] 1.2 g/m[2]/day for 6 months followed by maintenance lower doses of MMF 1-2 g/day or azathioprine [AZA] 2 mg/kg/day for 3 years have proven to be efficacy and less toxic than cyclophosphamide [CYC] therapy. Patients with membranous LN [Class V] plus diffuse or local proliferative LN [Class III and Class IV] should receive either the standard 6 monthly pulses of CYC [0.5-1 g/m[2]/month] then every 3[rd] month or to a shorter treatment course consisting of 0.5 g/m[2] IV CYC every 2 weeks for six doses [total dose 3 g] followed by maintenance therapy with daily AZA [2mg/kg/day] or MMF [0.6 g/m[2]/day] for 3 years. Combination of MMF plus rituximab or MMF plus calcineurin inhibitors may be an effective co-therapy for those refractory to induction or maintenance therapies. This report introduces a new treatment algorithm to prevent the development of ESRD in children with LN

Preventing kidney injury in children with neurogenic bladder dysfunction

The most common cause of neurogenic bladder dysfunction [NBD] in newborn infants is myelomeningocele. The pathophysiology almost always involves the bladder detrusor sphincter dyssynergy [DSD], which if untreated can cause severe and irreversible damage to the upper and lower urinary tracts. Early diagnosis and adequate management of NBD is critical to prevent both renal damage and bladder dysfunction and to reduce chances for the future surgeries. Initial investigation of the affected newborn infant includes a renal and bladder ultrasound, measurement of urine residual, determination of serum creatinine level, and urodynamics study. Voiding cystogram is indicated when either hydronephrosis or DSD is present. The main goal of treatment is prevention of urinary tract deterioration and achievement of continuance at an appropriate age. Clean intermittent catheterization [CIC] in combination with anticholinergic [oxybutynin] and antibiotics are instituted in those with high filling and voiding pressures, DSD and/or high grade reflux immediately after the myelomeningocele is repaired. Botulium toxin-A injection into detrusor is a safe alternative in patients with insufficient response or significant side effects to anticholinergic [oral or intravesical instillation] therapy. Surgery is an effective alternative in patients with persistent detrusor hyperactivity and/or dyssynergic detrusor sphincter despites of the CIC and maximum dosage of anticholinergic therapy. Children with NBD require care from a multidisciplinary team approach consisting of pediatricians, neurosurgeon, urologist, nephrologists, orthopedic surgeon, and other allied medical specialists

Hypomagnesemia an evidence-based approach to clinical cases

Hypomagnesemia is defined as a serum magnesium level less than 1.8 mg/dL [< 0.74 mmol/L]. Hypomagnesemia may result from inadequate magnesium intake, increased gastrointestinal or renal losses, or redistribution from extracellular to intracellular space. Increased renal magnesium loss can result from genetic or acquired renal disorders. Most patients with hypomagnesemia are asymptomatic and symptoms usually do not arise until the serum magnesium concentration falls below 1.2 mg/dL. One of the most life-threatening effects of hypomagnesemia is ventricular arrhythmia. The first step to determine the likely cause of the hypomagnesemia is to measure fractional excretion of magnesium and urinary calcium-creatinine ratio. The renal response to magnesium deficiency due to increased gastrointestinal loss is to lower.fractional excretion of magnesium to less than 2%. A fractional excretion above 2% in a subject with normal kidney function indicates renal magnesium wasting. Barter syndrome and loop diuretics which inhibit sodium chloride transport in the ascending loop of Henle are associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypercalciuria. Gitelman syndrome and thiazide diuretics which inhibit sodium chloride cotransporter in the distal convoluted tubule are associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypocalciuria. Familial renal magnesium wasting is associated with hypercalciuria, nephrocalcinosis, and nephrolithiasis. Asymptomatic patients should be treated with oral magnesium supplements. Parenteral magnesium should be reserved for symptomatic patients with severe magnesium deficiency [< 1.2 mg/dL]. Establishment of adequate renal function is required before administering any magnesium supplementation

Hypophosphatemia: an evidence-based problem-solving approach to clinical cases

Hypophosphatemia is defined as a serum phosphate level of less than 2.5 mg/dL [0.8 mmol/L]. Hypophosphatemia is caused by inadequate intake, decreased intestinal absorption, excessive urinary excretion, or a shift of phosphate from the extracellular to the intracellular compartments. Renal phosphate wasting can result from genetic or acquired renal disorders. Acquired renal phosphate wasting syndromes can result from vitamin D deficiency hyperparathyroidism, oncogenic osteomalecia, and Fanconi syndrome. Genetic disorders of renal hypophosphatemic disorders generally manifest in infancy and are usually transmitted as an X-linked hypophosphatemic rickets. Symptoms of hypophosphatemia are nonspecific and most patients are asymptomatic. Severe hypophosphatemia may cause skeletal muscle weakness, myocardial dysfunction, rhabdomyolysis, and altered mental status. The diagnostic approach to hypophosphatemia should begin with the measurement of fractional phosphate excretion; if greater than 15% in the presence of hypophosphatemia, the diagnosis of renal phosphate wasting is confirmed. Renal phosphate wasting can be divided into 3 types based upon serum calcium levels: primary hyperparathyroidism [high serum calcium level], secondary hyperparathyroidism [low serum calcium level], and primary renal phosphate wasting [normal serum calcium level]. Phosphate supplementations are indicated in patients who are symptomatic or who have a renal tubular defect leading to chronic phosphate wasting. Oral phosphate supplements in combination with calcitriol are the mainstay of treatment. Parenteral phosphate supplementation is generally reserved for patient with life-threatening hypophosphatemia [serum phosphate < 2.0 mg/dL]. Intravenous phosphate [0.16 mmol/kg] is administered at a rate of 1 mmol/h to 3 mmol/h until a level of 2 mg/dL is reached

Childhood Henoch-Schonlein nephritis: a multivariate analysis of clinical features and renal morphology at disease onset

Risk factors of renal involvement in Henoch-Schonlein nephritis [HSN] have been extensively studied, but their relations with the severity of glomerular lesions at the disease onset are much less known. Data were collected retrospectively on 45 patients [age range, 2 to 15 years] with HSN to identify the initial clinical and laboratory features that most accurately correlate with histological findings. Nephritic syndrome was defined as hypertension, proteinuria, hematuria, and a creatinine clearance of 60 mL/min/1.73 m[2] or less. Kidney biopsy findings were graded according to the International Study of Kidney Disease in Children classification for HSN. Purpura was present in all the 45 children, arthritis in 73.3%, abdominal symptoms with or without bleeding in 68.6%, and a high serum IgA level in 24.4%. Hematuria was present in 88.6% of the patients, hematuria and proteinuria [not in nephrotic range] in 66.7%, nephrotic syndrome in 17.8%, acute nephritic syndrome in 8.9%, and nephritic-nephrotic syndrome in 13.3%. Grades II [33.3%] and III [22.2%] lesions were the most common pathologic findings on kidney biopsy followed by grades IV [17.8%], V [15.6%], and I [11.1%] lesions. Univariate analysis demonstrated that nephrotic syndrome, acute nephritic syndrome and a creatinine clearance less than 30 mL/min/1.73 m2 were all associated with a significantly increased risk of developing grades IV and/or V lesions. multivariate analysis showed nephritic-nephrotic syndrome as significant independent predictors of severity of glomerular disease at onset

Hypercalcemia. An evidence-based approach to clinical cases

Primary hyperparathyroidism and malignancy are responsible for greater than 90% of all cases of hypercalcemia. Compared with the hypercalcemia of malignancy, hyperparathyroidism tends to be associated with lower serum calcium levels [< 12 mg/dL] and a longer duration of hypercalcemia [more than 6 months]. The hypercalcemic symptoms are usually fewer and subtle. Hyperparathyroidism tends to cause kidney calculi, hyperchloremic metabolic acidosis, and the characteristics of metabolic bone disease osteitis fibrosa cystica, but no anemia. In contrast, hypercalcemia of malignancy is typically rapid in onset, with higher serum calcium levels, and more severe symptoms. Patients so affected show marked anemia, but they never have kidney calculi or metabolic acidosis. Parathyroid hormone assay is the most useful test for differentiating hyperparathyroidism from malignancy and other causes of hypercalcemia. In hyperparathyroidism, serum parathyroid hormone levels will be elevated. In other cases, the high serum calcium concentration usually results in suppression of parathyroid hormone. Treatment of hypercalcemia should be started with hydration. Loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload. Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia. For long-term control of severe or symptomatic hypercalcemia, the addition of biphosphonate is typically required. Among intravenous bisphosphonates, zoledronic acid or pamidronate are the agents of choice. Glucocorticoids are effective in hypercalcemia due to lymphoma or granulomatous diseases. Dialysis is generally reserved for those with severe hypercalcemia complicated with kidney failure

Diagnosis of hypokalemia. A problem-solving approach to clinical cases

In situations where the cause of hypokalemia is not obvious, measurement of urinary potassium excretion and blood pressure and assessment of acid-base balance are often helpful. A random urine potassium-creatinine ratio [K/C] less than 1.5 suggests poor intake, gastrointestinal losses, or a shift of potassium into cells. If hypokalemia is associated with paralysis, we should consider hyperthyroidism, familial or sporadic periodic paralysis. Metabolic acidosis with a urine K/C ratio less than 1.5 suggests lower gastrointestinal losses due to diarrhea or laxative abuse. Metabolic acidosis with K/C ratio of 1.5 higher is often due to diabetic ketoacidosis or type 1 or type 2 distal renal tubular acidosis. Metabolic alkalosis with a K/C ratio less than 1.5 and a normal blood pressure is often due to surreptitious vomiting. Metabolic alkalosis with a higher K/C ratio and a normal blood pressure suggests diuretic use, Bartter syndrome, or Gitelman syndrome. Metabolic alkalosis with a high urine K/C ratio and hypertension suggests primary hyperaldosteronism, Cushing syndrome, congenital adrenal hyperplasia, renal artery stenosis, apparent mineralocorticoid excess, or Liddle syndrome. Hypomagnesemia can lead to increased urinary potassium losses and hypokalemia. The differential rests upon measurement of blood magnesium, aldosterone and renin levels, diuretic screen in urine, response to spironolactone and amiloride, measurement of plasma cortisol level and the urinary cortisol-cortisone ratio, and genetic testing

Vasoconstrictor-induced hypertension following multiple blood transfusions in children with congenital hemolytic anemia

The mechanism by which blood transfusion increases blood pressure in a substantial proportion of patients with congenital hemolytic anemia is unknown. Vascular endothelium dysfunction and increased endogenous vasoactive substances have been postulated in the pathogenesis of hypertension following multiple blood transfusions. The present study was undertaken to test the hypothesis whether increased circulating vasoconstrictors following blood transfusions, if documented, is a potent modulator of hypertension in patients with congenital anemia. Four children with congenital hemolytic anemia developed severe hypertension and convulsions 2 to 4 days after they received multiple blood transfusions. None had a history of prior hypertension, kidney disease or seizures before the blood transfusion. Baseline blood and urine samples were obtained for routine renal function studies. Blood samples were also drawn during and 2 weeks after the clinical events for determination of epinephrine, norepinephrine, dopamine, and plasma renin activity. Kidney function was normal in all the 4 patients. All had elevated plasma renin activity and increased blood epinephrine, norepinephrine, and dopamine concentrations during hypertensive crises. Hypertension responded to antihypertensive drugs with the patients remaining normotensive 3 to 6 days after commencing therapy. All recovered without further seizures. The elevated plasma renin activity, epinephrine, norepinephrine, and dopamine levels returned to reference levels 2 weeks after completion of the last blood transfusion. These data suggest that increased activity of vasoconstrictors in the recipient plasma may be responsible for the development of hypertension after multiple blood transfusions

Effects of prenatal alcohol exposure on the developing kidneys

Clinical and experimental studies strongly suggest that prenatal alcohol exposure is associated with zinc deficiency and impaired renal tubular function. Whether maternal alcohol consumption during pregnancy causes renal tubular cell injury is unknown. Renal function was studied in 8 infants with fetal alcohol syndrome [FAS] and 8 healthy age-matched infants. Renal function and structure were also examined in 11 offspring of rats exposed to alcohol during gestation. Infants with FAS had limited ability to concentrate urine after water restriction [P<0.001] and impaired acidification after acute acid loading [P<0.001] compared to control group. Plasma zinc levels were lower [P<0.001] and urinary zinc excretion was higher [P<0.001] in infants with FAS compared to control infants. Scanning electron microscopic studies revealed cytoplasmic mitochondrial hypertrophy and vacuolar structures of the epithelial cells of the cortical collecting ducts in the rat kidney following fetal exposure to alcohol. These findings suggest that offspring of rats exposed to alcohol during fetal life have renal functional and structural abnormalities that may be responsible in the genesis of renal functional abnormalities as described in infants with FAS

Approach to the patient with nephrolithiasis; the stone quiz

calcium oxalate stones are the most common type of stones in patients with idiopathic nephrolithiasis. A calcium phosphate stones are more typical of patients with renal tubular acidosis, chronic urinary tract infection and primary hyperparathyroidism. A non-contrast enhanced helical computed tomography [CT] scan of the abdomen is the diagnostic procedure of choice with superior sensitivity and specificity of almost 100% compared to the KUB and abdominal ultrasound. Patients should be instructed to strain their urine and bring in any stone that passes for analysis. Stone identification enables better planning of subsequent therapy. The likelihood of stone passage is 95% for stones up to 5 mm in size. Stones larger than 5 mm in diameter that do not pass in several days merit referral to an urologist for lithotripsy, or lithotomy. No specific work-up or drug therapy is typically provided for patients who have passed a single stone. Long term management of patients who have passed their first stone includes recommendations to avoid a diet high in salt or animal protein and maintenance of a fluid intake greater than 2 liters per day. A low calcium diet is also an important risk factor for calcium nephrolithiasis. A low dietary calcium intake reduces the concentration of calcium in the intestinal lumen which can lead to increase in gastrointestinal absorption and urinary excretion of oxalate Patient with recurrent disease should receive a complete evaluation to treat the identified risk factors and prevent stone formation