Renal tubular acidosis as the initial presentation of Sjögren's syndrome.

We present a 44-year-old female with an initial presentation with distal renal tubular acidosis (RTA) after she presented with hypokalaemia and normal anion gap acidosis. Three years following the diagnosis, she presented with progressive renal impairment. In the absence of any clinical, biochemical and radiological clues, she underwent a renal biopsy which showed severe tubulitis secondary to lymphocytic infiltration. Serological investigations subsequently revealed positive anti-nuclear, anti-Sjögren's syndrome related antigen A (SS-A), and anti-Sjögren's syndrome related antigen B (SS-B) antibodies, supporting the diagnosis of Sjögren's syndrome. This case is unique in that distal RTA was the presenting clinical manifestation of Sjögren's syndrome. We hope that a consideration for Sjögren's syndrome is made in patients with seemingly idiopathic RTA.

Hypokalemic Distal Renal Tubular Acidosis.

Distal renal tubular acidosis (DRTA) is defined as hyperchloremic, non-anion gap metabolic acidosis with impaired urinary acid excretion in the presence of a normal or moderately reduced glomerular filtration rate. Failure in urinary acid excretion results from reduced H+ secretion by intercalated cells in the distal nephron. This results in decreased excretion of NH4+ and other acids collectively referred as titratable acids while urine pH is typically above 5.5 in the face of systemic acidosis. The clinical phenotype in patients with DRTA is characterized by stunted growth with bone abnormalities in children as well as nephrocalcinosis and nephrolithiasis that develop as the consequence of hypercalciuria, hypocitraturia, and relatively alkaline urine. Hypokalemia is a striking finding that accounts for muscle weakness and requires continued treatment together with alkali-based therapies. This review will focus on the mechanisms responsible for impaired acid excretion and urinary potassium wastage, the clinical features, and diagnostic approaches of hypokalemic DRTA, both inherited and acquired.

Gitelman syndrome: an analysis of the underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities.

Gitelman syndrome is the most common inherited tubular disease resulting from mutations of the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter in the early distal convoluted tubules. The review presents the underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities observed in patients with Gitelman syndrome. The syndrome is usually characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Additionally, increased chloride excretion and renin/aldosterone levels, hypophosphatemia (occasionally), hyponatremia (rarely) and glucose intolerance/insulin resistance have been reported. The knowledge of the pathophysiologic mechanisms is useful for the treatment of patients with Gitelman syndrome as well as for the understanding of other tubular diseases.

Identification of the Causes for Chronic Hypokalemia: Importance of Urinary Sodium and Chloride Excretion.

BACKGROUND: Uncovering the correct diagnosis of chronic hypokalemia with potassium (K+) wasting from the kidneys or gut can be fraught with challenges. We identified clinical and laboratory parameters helpful for differentiating the causes of chronic hypokalemia. METHODS: Normotensive patients referred to our tertiary academic medical center for the evaluation of chronic hypokalemia were prospectively enrolled over 5 years. Clinical features, laboratory examinations-including blood and spot urine electrolytes, acid-base status, biochemistries, and hormones-as well as genetic analysis, were determined. RESULTS: Ninety-nine patients with chronic normotensive hypokalemia (serum K+ 2.8 ± 0.4 mmol/L, duration 4.1 ± 0.9 years) were enrolled. Neuromuscular symptoms were the most common complaints. Although Gitelman syndrome (n = 33), Bartter syndrome (n = 10), and distal renal tubular acidosis (n = 12) were the predominant renal tubular disorders, 44 patients (44%) were diagnosed with anorexia/bulimia nervosa (n = 21), surreptitious use of laxatives (n = 11), or diuretics (n = 12). Patients with gastrointestinal causes and surreptitious diuretics use exhibited a female predominance, lower body mass index, and less K+ supplementation. High urine K+ excretion (transtubular potassium gradient >3, urine K+/Cr >2 mmol/mmol) was universally present in patients with renal tubular disorders, but also found in >50% patients with gastrointestinal causes. Of interest, while urine sodium (Na+) and chloride (Cl-) excretions were high and coupled (urine Na+/Cl- ratio ∼1) in renal tubular disorders and "on" diuretics use, skewed or uncoupled urine Na+ and Cl- excretions were found in anorexia/bulimia nervosa and laxatives abuse (urine Na+/Cl- ratio: 5.0 ± 2.2, 0.4 ± 0.2, respectively) and low urine Na+ and Cl- excretions with fixed Na+/Cl- ratios (0.9 ± 0.2) when "off" diuretics. CONCLUSION: Besides body mass index, sex, and blood acid-base status, integrated interpretation of the urine Na+:Cl- excretion and their ratio is important to make an accurate diagnosis and treatment plan for patients with chronic normotensive hypokalemia.

[Unexplained chronic hypokalaemia in a young woman]. / Unklare chronische Hypokaliämie bei einer jungen Frau.

HISTORY AND CLINICAL FINDINGS: The 27 year old female patient presented with chronic hypokalaemia known for 6 years and current potassium values of 1.8 mmol/l. She reported having diarrhea for a few days, fever was denied. INVESTIGATIONS: Physical examination revealed dry skin and mucosa and a slim nutritional status, laboratory investigations showed a hypokalaemic, hypochloraemic alkalosis and hypomagnesaemia. Our first suspicion was an eating disorder or abuse of diuretics or laxatives. Urine analysis showed a high concentration of potassium and chloride, a screening for diuretics was negative. Due to the electrolyte constellation we assumed a Gitelman's Syndrome which was confirmed by genetic testing. TREATMENT AND COURSE: After intravenous substitution of potassium and cessation of diarrhea the potassium values stabilised at 2.5 - 3.0 mmol/l. After being discharged she continued oral substitution of potassium and no such period of severe hypokalaemia occurred again. CONCLUSION: Establishing a diagnosis for patients with chronic hypokalaemia may present difficulties. Urine analysis can help to find reasons for electrolyte disorders. Via measurement of urinary chloride concentration repetitious vomiting as stigmatising diagnosis could be excluded. Urine analysis also led to the diagnosis Gitelman syndrome, an inherited renal tubular disorder, which is suspected to count for 50 % of unexplained chronic hypokalemia.

Electrolyte disturbances and abnormal urine analysis in children with dengue infection.

Serum electrolytes and urine analysis results were retrospectively reviewed in children with either dengue fever (DF) or dengue hemorrhagic fever (DHF). Children who had positive serology for dengue infection and serum electrolytes determined before starting intravenous fluid were included in the study. During the years 2004-2007, 73 DF patients, age 9.29 +/- 3.62 years, and 77 DHF patients, age 10.04 +/- 3.64 years were enrolled in the study. The patients were admitted to the hospital on average on days 4.12 +/- 1.1 and 4.25 +/- 1.4 of febrile illness for DF and DHF, respectively. The prevalence of hyponatremia in patients with DF was 61% and DHF was 72% (p = 0.149). The mean serum sodium levels in patients with DF and DHF were 133.5 +/- 3.52 and 133.5 +/- 3.20 mEq/l (p = 0.938), respectively. The prevalence of hyponatremia in patients with mild (grade I), moderate (grade II) and severe (grade III-IV) DHF were 70, 77, and 78% (p = 0.729), respectively, and the mean serum sodium levels were 134.1 +/- 3.05, 132.9 +/- 3.33, and 132.5 +/- 3.28 (p = 0.189), respectively. The prevalence of hypokalemia in patients with DF was 14% and 17% in patients with DHF (p = 0.588). A high urine specific gravity reflecting dehydration was found in 63% of patients with DF and 60% of patients with DHF (p = 0.77). The prevalences of hematuria in patients with DF and DHF were 18% and 27% (p = 0.182), respectively and proteinuria were 15% and 27% (p = 0.072), respectively. The prevalences of hematuria and proteinuria were not different among patients with mild, moderate and severe DHF. No patients had gross hematuria or developed acute renal failure requiring dialysis. Mild hyponatremia is a common electrolyte disturbance and renal involvement is mild in patients with DF and DHF.

Proteinuria lowers the risk of amphotericin B-associated hypokalaemia.

OBJECTIVES: Amphotericin B-induced nephrotoxicity is frequent, severe and associated with an increased risk of death. Patients with underlying renal disease are considered to be at high risk for amphotericin B nephrotoxicity. Amphotericin B is a molecule that is highly protein bound over a wide range of protein and drug concentrations, including those seen in patients with >or= 3 + proteinuria. We hypothesized that amphotericin B treatment in patients with proteinuria will be associated with less hypokalaemia than patients with non-proteinuric renal disease. METHODS: Thirty-six subjects who received amphotericin B deoxycholate were studied retrospectively. Twenty-five patients with proteinuria < 3 g/L and 11 with proteinuria >or= 3 g/L were compared. RESULTS: Hypokalaemia (K+ < 3.5 mmol/L) developed in 47.2% (17/36) of our cohort of patients. There was a 64% (16/25) incidence of hypokalaemia in the group with < 3 g/L of proteinuria in contrast to an incidence of 9.1% (1/11) in the other group. CONCLUSIONS: In our study, heavy proteinuria appears to protect the tubular luminal membrane by decreasing the luminal concentration of free drug available to bind with the membrane. Our findings redefine the patient population deemed to be at risk of developing amphotericin B nephrotoxicity. This ensures the benefit of this important antifungal treatment option to patients with heavy proteinuria who might otherwise not be administered this drug due to the presence of pre-existing kidney disease.

Hypocalciuria in patients with Gitelman syndrome: role of blood volume.

BACKGROUND: Hypocalciuria is common in patients with Gitelman syndrome (GS), and its cause primarily is enhanced renal reabsorption of calcium in the proximal tubule in response to hypovolemia, judged by recent studies in animals. STUDY DESIGN: Uncontrolled trial in cases and controls to evaluate the effect of acute reexpansion of extracellular fluid volume (ECFV) on urine calcium excretion in patients with GS. SETTING & PARTICIPANTS: 8 patients with GS and 8 sex- and age-matched healthy control subjects (CSs) were enrolled in an academic medical center. PREDICTOR: ECFV expansion with isotonic saline at 1 L/h for 3 hours. OUTCOMES & MEASUREMENTS: Urinary calcium excretion was measured hourly for 6 hours, and subsequent 18-hour urine was analyzed as a single collection; hormones and electrolytes were measured. RESULTS: Patients with GS had hypokalemia, metabolic alkalosis, hypomagnesemia, severe hypocalciuria (urine calcium-creatinine ratio, 0.006 +/- 0.002 versus 0.08 +/- 0.02 mg/mg [0.02 +/- 0.01 versus 0.22 +/- 0.05 mmol/mmol]; P < 0.005), and a mild degree of ECFV contraction. Sodium excretion and creatinine clearance rates were similar to those in CSs. In patients with GS, saline infusion increased ECFV, which caused a significantly greater sodium excretion rate, but there was only a small increase in calcium excretion rate, in both the first 6 hours (0.04 +/- 0.02 mg/min [1.0 +/- 0.6 micromol/min]) and subsequent 18-hour period (0.02 +/- 0.01 mg/min [0.4 +/- 0.2 micromol/min]), as in CSs. Notwithstanding, their calcium excretion rate was still much less than that in CSs before volume repletion (0.13 +/- 0.04 mg/min [3.2 +/- 1.0 micromol/min]). LIMITATION: Patients with GS did not become euvolemic on a long-term sodium chloride supplementation because they excreted sodium chloride so rapidly. CONCLUSION: Hypovolemia is not the sole cause of hypocalciuria in patients with GS.

An approach to the patient with severe hypokalaemia: the potassium quiz.

The objective of this teaching session with Professor McCance is to develop an approach to the management of patients with a very low plasma potassium (K(+)) concentration (P(K)). The session begins with a quiz based on six recent medical consultations for a P(K) < 2 mmol/l. Professor McCance outlined how he would proceed with his diagnosis and therapy, using the synopsis that described each patient. This approach was then applied to a new patient, a 69-year-old woman who had a large volume of dependent oedema and developed a severe degree of weakness and hypokalaemia during more aggressive diuretic therapy that included a K(+)-sparing diuretic. The initial challenge for Professor McCance was to deduce why the K(+)-sparing diuretic was not effective in this patient. He also needed to explain why the P(K) was so low on admission.