Chronic kidney disease score for predicting postoperative masked renal insufficiency in patients with primary aldosteronism.

CONTEXT: Chronic kidney disease (CKD) is sometimes unmasked after unilateral adrenalectomy in patients with primary aldosteronism (PA) without expectation. OBJECTIVE: Our study aim was to elucidate factors responsible for developing postoperative CKD and to provide a simple scoring system to predict postoperative CKD in PA. DESIGN AND PATIENTS: Forty-five patients with PA treated with unilateral adrenalectomy and followed for at least 1 month postsurgery were studied. Thirty-one patients with non-PA adrenal disease who underwent unilateral adrenalectomy were also studied as control. Patients with pre-operative estimated glomerular filtration rate (eGFR) < 60 ml/min/1·73 m(2) were excluded from both groups. RESULTS: A statistically significant (P < 0·001) decrease in eGFR was observed in PA group within 1 month of surgery, then stabilized. Of the 45 patients with PA, 17 (37·8%) developed CKD after surgery. None of the non-PA group developed CKD after surgery. Of the pre-operative variables, logistic regression analysis showed that lower eGFR and higher aldosterone-to-renin ratios (ARR) were the independent predictors for postoperative CKD in PA. Optimal cut-off values of the two variables analysed with ROC curves were as follows: eGFR ≤ 76·9 ml/min/1·73 m(2) and ARR ≥ 305. Using these data, we created a CKD score as a tool for predicting postoperative CKD, with an AUC for the score of 0·8866. CONCLUSION: The pre-operative eGFR and ARR were the significant contributing factors for postoperative CKD in PA. By combining these independent factors, we created a CKD score which provides useful information before surgery about the risk for development of postoperative CKD.

Nephrogenic diabetes insipidus associated with hemochromatosis.

Although hemochromatosis is one of the most common genetic disorders in humans, the clinical information on iron-induced renal impairment is limited. We describe the clinical features of nephrogenic diabetes insipidus (NDI) observed in a case of hemochromatosis. A 57-year-old diabetic man was admitted to the hospital with a 6-month history of persistent polyuria, which had been sustained after glycemic optimization with insulin therapy and resulted in hepatic coma. Despite sufficient basal excretion of arginine vasopressin, impaired urinary concentrating capacity was observed, which could not be corrected by supraphysiologic doses of exogenous arginine vasopressin. Histochemical investigations showed widely distributed iron deposition in hepatocytes and moderately increased iron deposits in the tubular epithelium of distal urinary tubules and collecting ducts, suggesting that iron deposition resulting from hemochromatosis leads to NDI. This may be the first case report of NDI associated with hemochromatosis in humans. More attention should be paid to latent NDI as another complication of hemochromatosis.

Urine output and resultant osmotic water shift are major determinants of plasma sodium level in syndrome of inappropriate antidiuretic hormone secretion.

Although various formulas predicting plasma sodium level ([Na]) are proposed for correction of hyponatremia, it seems that an anticipated [Na] frequently exceeds or falls below the measured [Na], especially in syndrome of inappropriate antidiuretic hormone secretion (SIADH). The causative factors of the fluctuation have never been investigated clearly. The aim of this study was to identify the determining factors for accurate prediction of [Na] by comparing data from previously proposed formulas and a novel osmotic compartment model (O-C model). The O-C model, which simulates the amounts of osmoles in extracellular and intracellular fluids, can estimate resultant osmotic water shift (OWS) and [Na]. The accuracy of representative formulas was verified in a point-to-point study using blood and urine samples obtained every 4 hours from 9 patients. Among 161 measurement points, a large fluctuation of urine volume and urine sodium level was observed. The gap between anticipated and measured [Na] in the widely used Adrogue-Madias formula was -0.5 ± 0.1 mEq/L/4 h (mean ± standard error), showing a marked tendency to underestimate [Na]. The gap in the O-C model including OWS was 0.1 ± 0.1 mEq/L/4 h, and that in the O-C model eliminating OWS was 1.9 ± 0.2 mEq/L/4 h, indicating that measurement of urine output and estimation of resulting OWS are essential for a superior prediction of [Na] in SIADH. A simulation study with the O-C model including OWS unveiled a distinctive correction pattern of [Na] dependent on the urine volume and urine sodium level, providing a useful choice for the proper type and rate of infusion.

Histopathological diagnosis of primary aldosteronism using CYP11B2 immunohistochemistry.

CONTEXT: Although primary aldosteronism (PA) is the most common cause of endocrine hypertension, histopathological methods to reveal the presence and sites of aldosterone overproduction remain to be established. OBJECTIVE: The objective of the study was to investigate the significance of immunohistochemical staining to detect CYP11B2 and CYP11B1 in adrenal tissue of patients with PA. DESIGN AND PATIENTS: Thirty-two patients with PA who underwent unilateral adrenalectomy were studied. Immunohistochemical staining was performed using anti-CYP11B2 and anti-CYP11B1 antibodies on paraffin-embedded sections. We analyzed the expression of each enzyme semiquantitatively by scoring staining intensity and correlating it with clinical findings. RESULTS: Twenty-two patients showed positive CYP11B2 immunostaining in their tumors (aldosterone producing adenoma, APA). Four patients with CYP11B2-negative unilateral adenomas and 4 patients without tumors on computed tomography showed aldosterone-producing cell clusters (APCCs) with CYP11B2 immunostaining in the zona glomerulosa (multiple APCCs). The remaining 2 patients had unilateral multiple adrenocortical micronodules and diffuse adrenocortical hyperplasia, respectively. In APA, CYP11B2 score adjusted for tumor volume was positively correlated with plasma aldosterone and negatively correlated with serum potassium. The APA group was divided into 3 subgroups based on relative CYP11B2 and CYP11B1 immunostaining levels. The CYP11B2/CYP11B1-equivalent and CYP11B1-dominant APA groups showed significantly higher serum cortisol after 1 mg dexamethasone and larger tumor size than the CYP11B2-dominant APA group. CONCLUSIONS: The present study clearly demonstrates that CYP11B2 immunostaining is a powerful tool for histopathological diagnosis of aldosterone overproduction in PA and for subtype classification of APA, multiple APCCs, unilateral multiple adrenocortical micronodules, and diffuse hyperplasia.

Central diabetes insipidus and hypothalamic hypothyroidism associated with aceruloplasminemia.

Aceruloplasminemia is a rare autosomal recessive disease first reported by Miyajima et al. (Neurology 37: 761-767, 1987); it is clinically characterized by diabetes mellitus, retinal degeneration and neurological abnormalities, such as cerebellar ataxia, extrapyramidal signs and dementia. Aceruloplasminemia is caused by mutations in the ceruloplasmin gene, which results in the absence of serum ceruloplasmin and iron overload in the brain, liver, pancreas and other organ tissues. However, little is known about endocrine diseases associated with aceruloplasminemia. We report herein a case of aceruloplasminemia accompanied by central diabetes insipidus and hypothalamic hypothyroidism.