Acute Tubular Injury Associated with Mesalazine Therapy in an Adolescent Girl with Inflammatory Bowel Disease

Mesalazine is a first-line drug in pediatric inflammatory bowel disease, and is effective as primary treatment and maintenance therapy. It’s usually well tolerated, but various side effects have been described. A 15-year-old female with ulcerative colitis developed polyuria, polydipsia, vomiting, and fatigue. She was receiving mesalazine (500 mg, thrice daily, p.o.) and prednisolone for 4 months. She was detected as acute tubular injury as she had dehydration, acidosis, hypostenuria, hematuria, proteinuria, low levels of potassium, uric acid and bicarbonate. These findings were attributed to interstitial nephritis as a side effect of mesalazine, however as renal biopsy was disapproved by the parents, it was not confirmed. After discontinuation of mesalazine her renal tubular functions improved. Potassium and phosphorus supplements were stopped after 7 months, although she had to continue bicarbonate supplementation. We conclude that regular renal screening is important in patients receiving 5-ASA therapy to prevent rare but serious complications, such as interstitial nephritis sometimes leading to chronic renal failure.     

Reduced nephrotoxicity of conventional amphotericin B therapy after minimal nephroprotective measures: animal experiments and clinical study

Amphotericin B (AmB)-treated rats develop severe polyuria, polydypsia, impairment of renal concentrating ability, and morphologic signs of tubular damage. However, renal insufficiency develops quickly only in animals in which water intake is restricted to the median volume drunk by rats of the control group. Therefore, vigorous hydration seems crucial for prevention of AmB-induced nephrotoxicity. In a clinical study, 61 patients with hematologic malignancies receiving AmB therapy were massively hydrated to ensure urine output of > or =4000 mL/day. Urine sodium, potassium, and magnesium were also measured, and all losses were supplemented (potassium as a 7.45% solution via central venous catheter). AmB-treated patients developed signs of renal tubular damage (increased fractional excretion of sodium and potassium) and required large amounts of ion supplementation. The serum ion concentration and creatinine clearance remained stable. No clinically significant renal damage developed to force premature cessation of AmB treatment.     

A case of Sjögren’s syndrome presenting as hypokalemic myopathy due to distal renal tubular acidosis

We report a case of hypokalemic myopathy with distal renal tubular acidosis which leads to the diagnosis of Sjögren’s syndrome (SS). A 67-year-old man was admitted to our department for progressive muscle weakness and myalgia. Laboratory data demonstrated hypokalemia with hyperchloremic acidosis, elevated muscle enzyme and inability to acidify urine. Findings of interstitial nephritis, which is consistent with renal tubular acidosis in SS, were found on renal biopsy. Remarkable changes of the renal tubule, including tubular atrophy, dilatation and intratubular casts, were observed. Potassium replacement therapy normalized the marked elevated urinaryβ ₂-microglobulin excretion as well as the improvement of muscle symptoms. Taken together with our findings, it it suggested that sustained hypokalemia may partly contribute to the exacerbation of the pre-existing renal tubular disorder in SS.     

A case of Sjögren’s syndrome presenting as hypokalemic myopathy due to distal renal tubular acidosis

Abstract

We report a case of hypokalemic myopathy with distal renal tubular acidosis which leads to the diagnosis of Sjögren’s syndrome (SS). A 67-year-old man was admitted to our department for progressive muscle weakness and myalgia. Laboratory data demonstrated hypokalemia with hyperchloremic acidosis, elevated muscle enzyme and inability to acidify urine. Findings of interstitial nephritis, which is consistent with renal tubular acidosis in SS, were found on renal biopsy. Remarkable changes of the renal tubule, including tubular atrophy, dilatation and intratubular casts, were observed. Potassium replacement therapy normalized the marked elevated urinary β₂-microglobulin excretion as well as the improvement of muscle symptoms. Taken together with our findings, it it suggested that sustained hypokalemia may partly contribute to the exacerbation of the pre-existing renal tubular disorder in SS.     

Hypokalemic periodic paralysis in Sjogren’s syndrome secondary to distal renal tubular acidosis

We report a 53-year-old Turkish female presented with progressive weakness and mild dyspnea. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis. The urinary anion gap was positive in the presence of acidemia, thus she was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:3,200 and positive antibodies to SSA and SSB. Schirmer’s test was abnormal. Autoimmune and other tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Renal involvement in Sjogren’s syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy, and corticosteroids. Primary SS could be a differential in women with acute weakness and hypokalemia.     

Cystinosis presenting with findings of Bartter syndrome

A five-year-old boy was referred to our pediatric clinic for evaluation of failure to thrive, headache, intermittent high fever, restlessness, polyuria, and polydipsia. His weight and height measurements were under the 3rd percentile. Clinical findings consisted of frontal bossing, carious teeth, O-bain deformity of the lower extremities, and moderate dehydration. The presence of metabolic alkalosis, hypokalemia, hypochloremia, and high renin and aldosterone levels were suggestive of Bartter syndrome and a treatment regimen for Bartter syndrome was started. At follow-up, the polyuria and hyponatremia were found to persist. A reassessment of the patient revealed findings consistent with proximal renal tubular acidosis such as metabolic acidosis with a high urinary pH, proteinuria, aminoaciduria with phosphaturia and hypercalciuria. Based on the presence of parental consanguinity as well as polyuria, proteinuria, low tubular reabsorption of phosphorus, generalized aminoaciduria, light yellow skin and hair color, the probable diagnosis of cystinosis was established and was confirmed by slit-lamp examination of the cornea showing cystine crystal deposition. Our case is a good example demonstrating that development of metabolic alkalosis does not exclude cystinosis and that all findings of the patient should be thoroughly evaluated.     

Renal potassium wasting in distal renal tubular acidosis: role of aldosterone.

The pathogenesis of renal potassium wasting and hypokalemia in classic renal tubular acidosis (type 1 RTA) remains uncertain. The prevailing theory is that K(+)-Na+ exchange is stimulated due to an inability of the distal tubule to establish a normal steep lumen-peritubular H+ gradient. We encountered a 42-year-old woman with type 1 RTA associated with Sj?gren's syndrome, in whom renal potassium wasting and hypokalemia persisted despite sustained correction of systemic acidosis with alkali therapy and increased intake of potassium. In addition, plasma renin activity was markedly increased and the serum aldosterone level was upper-normal despite the hypokalemia. Increased intake of sodium resulted in suppression on the serum aldosterone and correction of renal potassium wasting and hypokalemia. This case shows that secondary hyperaldosteronism, possibly due to an impairment of sodium conservation in the distal tubule, may contribute to the loss of potassium from the distal tubule even after the correction of acidosis.     

Non-psychogenic primary polydipsia in autoimmune chronic active hepatitis with severe hyperglobulinaemia.

The association of hyperglobulinaemia with renal tubular acidosis and nephrogenic diabetes insipidus is well established. A patient with marked hyperglobulinaemia due to autoimmune chronic active hepatitis is described who presented with severe polydipsia and polyuria but had entirely normal renal tubular function indicating a primary thirst disorder.     

Hypokalemic paralysis associated with distal renal tubular acidosis.

A 68-year-old man had hydronephrosis due to ureteral stones for two months earlier and then increasing muscle weakness developed. A 30-year-old woman had rapidly progressive quadriparesis. In both cases, severe hypokalemia with metabolic acidosis was observed and the diagnosis of distal renal tubular acidosis was made. The former was considered to be an idiopathic incomplete form and the latter was a secondary complete form associated with Sj?gren syndrome. Hypokalemic paralysis may occur as a complication of distal renal tubular acidosis.     

Life-threatening hypokalaemic paralysis associated with distal renal tubular acidosis

A 56-year-old woman developed acute respiratory failure requiring mechanical ventilation due to acute hypokalaemic paralysis. There was no gastrointestinal potassium loss nor was she taking diuretics. Additional analyses revealed a normal anion gap metabolic acidosis with a positive urine anion gap. An acid-load test revealed a renal urine acidification defect, leading to the diagnosis of distal renal tubular acidosis. Normalisation of serum potassium level was established with oral bicarbonate supplementation and temporary potassium supplementation.     

Life-threatening hypokalemia following rapid correction of respiratory acidosis

A 56-year-old woman with a history of paraplegia and chronic pain due to neuromyelitis optica (Devic's syndrome) was admitted to a spinal cord injury unit for management of a sacral decubitus ulcer. During the hospitalization, she required emergency transfer to the intensive care unit (ICU) because of progressive deterioration of respiratory muscle function, severe respiratory acidosis, obtundation and hypotension. Upon transfer to the ICU, arterial blood gas revealed severe acute-on-chronic respiratory acidosis (pH 7.00, PCO₂ 120 mm Hg, PO₂ 211 mm Hg). The patient was immediately intubated and mechanically ventilated. Intravenous fluid boluses of normal saline (10.5 L in about 24 h) and vasopressors were started with rapid correction of hypotension. In addition, she was given hydrocortisone. Within 40 min of initiation of mechanical ventilation, there was improvement in acute respiratory acidosis. Sixteen hours later, however, the patient developed life-threatening hypokalemia (K⁺ of 2.1 mEq/L) and hypomagnesemia (Mg of 1.4 mg/dL). Despite aggressive potassium supplementation, hypokalemia continued to worsen over the next several hours (K⁺ of 1.7 mEq/L). Urine studies revealed renal potassium wasting. We reason that the recalcitrant life-threatening hypokalemia was caused by several mechanisms including total body potassium depletion (chronic respiratory acidosis), a shift of potassium from the extracellular to intracellular space (rapid correction of respiratory acidosis with mechanical ventilation), increased sodium delivery to the distal nephron (normal saline resuscitation), hyperaldosteronism (secondary to hypotension plus administration of hydrocortisone) and hypomagnesemia. We conclude that rapid correction of respiratory acidosis, especially in the setting of hypotension, can lead to life-threatening hypokalemia. Serum potassium levels must be monitored closely in these patients, as failure to do so can lead to potentially lethal consequences.     

Obstructive polyuric renal failure following renal transplantation

In a previously nephrectomized patient with a well functioning renal allograft, acute renal failure with massive polyuria and hypertension developed. Relief of a periureteric obstruction resulted in rapid correction of all three. Pathogenesis of hypotonic polyuria is thought to be a defect in the collecting duct permeability to water, simulating nephrogenic diabetes insipidus. Normal urinary dilution and acidification suggest intact function of the ascending loop of Henle and distal convoluted tubules. The quick reversal of polyuria and renal failure after obtaining relief of the obstruction suggest that both the decrease in the glomerular filtration rate and tubular dysfunctions are due to functional changes in the nephron rather than to organic damage, a possibility also borne out by the findings in a renal biopsy specimen showing normal glomeruli and intact tubular epithelial cells. Ureteric obstruction should be considered in any patient with renal failure and polyuria; it may be a correctable cause of hypertension.     

范可尼综合征的临床特点与生化异常

目的 进一步认识范可尼综合征（FS）的病因、临床特点与生化异常。方法 对我院确诊的42例FS患者进行回顾性分析。结果 42例FS中完全型19例，不完全型23例，主要表现为近端肾小管酸中毒（41例）伴物质转运异常，包括低钾血症（21例）、低磷血症（29例）、低尿酸血症（19例）、肾性糖尿（38例）、氨基酸尿（36/37例）和低分子蛋白尿（21例）。病因：特发性或原因不明21例，继发性21例；其中间质性肾炎8例，干燥综合征5例。临床表现以乏力、多饮、多尿、肾性骨病最常见，伴肾功能不全者18例。14例患者接受肾活检，结果均显示有不同程度的小管-间质病变，其中4例伴有肾小球病变。结论 FS病因多样，继发性FS并不少见，一般均伴有Ⅱ型肾小管酸中毒，并常有肾小管-间质的病理损害。     

Tétraparésie hypokaliémique révélant un syndrome de Gougerot-Sjögren

We report a 30-year-old woman who presented with a hypokaliemia-related subacute quadriparesis. The various causes of hypokalemia induced paresis were discussed but the association of hypokalemia with metabolic acidosis and normal anion gap was diagnostic of distal renal tubular acidosis. The renal tubulopathy was the presenting manifestation of a primary Sjogren's syndrome. Distal renal tubular acidosis concerns a third of the patients affected by this auto-immune disease.     

Hypokalemia induced quadriparesis as the presenting manifestation of Gougerot-Sjögren's syndrome

We report a 30-year-old woman who presented with a hypokaliemia-related subacute quadriparesis. The various causes of hypokalemia induced paresis were discussed but the association of hypokalemia with metabolic acidosis and normal anion gap was diagnostic of distal renal tubular acidosis. The renal tubulopathy was the presenting manifestation of a primary Sjogren's syndrome. Distal renal tubular acidosis concerns a third of the patients affected by this auto-immune disease.     

Simultaneous clinical resolution of focal segmental glomerulosclerosis associated with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab

Background

Severe hypokalemia is known to cause muscle paralysis, and renal tubular acidosis is a recognized cause. Cystic disease of the kidney is associated with severe hypokalemia.

Case presentation

We report a 33-year-old male patient who presented with generalized limb weakness caused by severe hypokalemia due to renal tubular acidosis, who was found to have renal medullary cysts.

Conclusion

The association of cystic renal disease with hypokalemia, and the possible pathophysiological basis of the development of renal cysts in patients with severe hypokalemia, are discussed.     

Familial hyperkalemia, hypertension, and hyporeninemia with normal aldosterone levels. A tubular defect in potassium handling

A 52-year-old man had hypertension, persistent hyperkalemia, and hyperchloremic metabolic acidosis; renal and adrenal functions were normal. Four other members of the family have the same findings. The patient's plasma aldosterone (PA) level was within normal range, though plasma renin activity (PRA) was undetectable. The ability to conserve sodium with increased endogenous aldosterone levels, and the inability to increase potassium excretion while exogenous mineralocorticoid (fludrocortisone acetate) was administered, indicated a distal tubular defect in potassium handling. Effective reduction of the hyperkalemia by K+ -Na+ exchange resin also corrected the acidosis and the hyperchloremia, suggesting that hyperkalemia may cause metabolic acidosis.     

Distal renal tubular acidosis in HIV/AIDS patient

We report a case of renal tubular acidosis (RTA) in a patient with HIV infection and AIDS. A 33-year-old HIV-positive man with Hepatitis C and tuberculous lymphadenitis was admitted due to deep venous thrombosis and generalized muscle weakness. He had never received anti-retroviral medication. The blood gases and serum electrolytes showed hyperchloremic normal anion gap metabolic acidosis with severe hypokalemia and alkaline urine. Diagnosis of distal RTA was made. His renal function and serum globulin level remained within normal range throughout his illness. Clinicians should be alert to renal tubular disorders in HIV/AIDS patients even in the absence of anti-retroviral therapy or hypergammaglobulinemic state.     

Hypokalemic paralysis and osteomalacia secondary to renal tubular acidosis in a case with primary Sjögren's syndrome

A 39-year-old Japanese woman was admitted to our hospital for severe weakness owing to potassium deficiency caused by type 1 renal tubular acidosis (RTA1). Sicca complex, serological tests, and lip biopsy revealed that she had Sjögren's syndrome (SS). Acidosis was corrected by alkali supplement treatment. She also had an impaired renal function with proteinuria, and high absorbance on Ga scintigram was recognized in both kidneys. She was taking warfarin potassium after aortic valve substitution due to aortic regurgitation, therefore renal biopsy was not performed. Prednisone (20?mg/day) was administered for renal inflammation. One month later, she suffered severe chest wall pains with some local tender points over the costae of both sides, which was presumed to be due to pseudofractures based on osteomalacia. Hypokalemic paralysis and osteomalacia should be taken into consideration in the diagnosis of SS with RTA1.