INTERNATIONAL JOURNAL OF CLINICAL AND MEDICAL CASES (ISSN:2517-7346)

Hypokalemia is universally present in patients with Bartter syndrome. The case presented here with Bartter syndrome and persistent severe hypokalemia revealed unique pathological findings on renal biopsy. Prolonged hypokalemia is related to renal injury, but cause may differ. These findings included: mesangial sclerosis, patchy tubular atrophy, interstitial fibrosis, mononuclear infiltration, as well as thickening of tubular basement membrane. Tubular epithelium revealed focal loss of apical brush border. Typically observed tubular cell vacuolization or presence of renal cysts that are frequently reported, were absent in the case. Kaleopenic nephropathy is associated with eating disorders and laxative abuse among other causes of chronic hypokalemia in patients. Severe renal function impairment requiring dialysis has been previously reported. Juxtaglomerular apparatus hyperplasia noted in our case has been reported in Bartter syndrome, renal ischemia, and cyclosporin use. Despite the fact that Keleopenic nephropathy has disappeared from literature in the past 20 years, we believe the condition still exists.

Bartter syndrome; Kaleopenic nephropathy; Hypokalemia 

Hypokalemia-induced renal changes, or kaliopenic nephropathy, was first mentioned in 1956 by JW Conn to describe structural and physiological changes found in renal tubules due to a significant drop in serum potassium, induced by hypermineralcorticoidism [1]. If potassium depletion is prolonged enough, as seen in Bartter syndrome, characteristic lesions can be noted, Table 1 [2,3]. Most pronounced changes in our case were the presence of mesangial sclerosis along with interstitial fibrosis and tubular atrophy, but typical association of tubular vacuolization or cyst formation were absent, thus it is understandable these findings were brought upon by hypokalemia rather than Bartter syndrome. Other typical findings observed include ammoniagenesis [4], increased bicarbonate reabsorption [5] leading to metabolic alkalosis, as well as an impaired ability to concentrate urine [6].

Bartter syndrome is a rare disorder of the nephron that can occur sporadically or can be inherited in an autosomal recessive pattern. The most striking primary defect seems to be in the reabsorption of chloride in the loop of Henle (thick ascending limb) even though the primary defect has been debated thru the years ever since FC Bartter had first described the syndrome in 1962 [2]. The defect in chloride reabsorption can impair passive reabsorption of potassium as well as sodium at the same site [7]. Classic signs and symptoms of this syndrome include polydipsia, polyuria, and decreased urine concentrating ability [8]. Features of this syndrome are hypokalemia, hypochloremic metabolic alkalosis, hyperreninemia, hyperaldosteronism, normal to mildly reduced serum magnesium, and normal to low blood pressure. The most distinguishing and consistent pathological finding in Bartter syndrome is the hyperplasia of the juxtaglomerular apparatus, irreversible even if given a potassium-sparing diuretic [9]. Current treatments include potassium supplementation and potassium-sparing diuretics. Renin inhibitors and angiotensin converting enzyme-inhibitors have also been utilized in the treatment of this particular syndrome [10].

A 37 year old female with history of Bartter syndrome presented with severe persistent hypokalemia. Physical examination was unremarkable. Laboratory findings revealed potassium 2.3 mEq/L, chloride 87 mEq/L, CO2 38 mmol/L, renin 13.6, aldosterone 11.6, magnesium 2.2 mg/dL, and GFR 41 ml/min. This patient’s blood pressure has been consistently normal with the systolic ranging from 100 to 115 mmHg and the diastolic pressure ranging from 50 to 70 mmHg. Urinalysis was performed and revealed normal results. Her medications included Spironolactone and potassium chloride. Despite treatment with a potassium-sparing diuretic and potassium supplementation, patient’s serum potassium level remained depressed.

A renal ultrasound revealed bilaterally normal sized kidneys with thin cortices.

A renal biopsy was performed and revealed the following (read by Dr. M. Barry Stokes of NY Presbyterian/Columbia University Irving Medical Center, NYC):

Upon staining with hematoxylin & eosin (H&E), periodic acidSchiff (PAS), trichrome, and Jones methenamine silver (JMS), there was an observation of hyperplasia of the juxtaglomerular apparatus. Patchy tubular atrophy and interstitial fibrosis with mononuclear inflammatory infiltrates were noted. There was absence of tubular vacuolization and cyst formation. Biopsy also revealed tubular epithelium with focal loss of apical brush border.

Mesangial sclerosis and thickening of tubular basement membranes were seen (Figure 1 A). Tubules exhibiting basement membrane thickening and atrophy of tubular cells (Figure 1B). Interstitial collagen and rare interstitial mononuclear inflammatory cells were also noted (Figure 2). Immunofluorescence examination was negative.