Primary aldosteronism: changes in cystatin C-based kidney filtration, proteinuria, and renal duplex indices with treatment.

OBJECTIVES: To obtain information about the effect of prolonged aldosterone excess on kidney function. METHODS: We determined kidney function changes defined by cystatin C-based estimations of glomerular filtration rate (CysC-GFR). Pretreatment proteinuria and intrarenal Doppler velocimetric indices in primary aldosteronism were examined and followed after adrenalectomy or spironolactone treatment. RESULTS: This prospective, multicenter study included 130 primary aldosteronism patients (56 men; age, 49.9 ± 13.4 years: 100 with adenoma and 30 with idiopathic hyperaldosteronism) and 73 essential hypertension patients (36 men; age, 51.4 ± 14.8 years) as controls. Patients with primary aldosteronism had higher CysC-GFR (P < 0.05) and heavier proteinuria (0.042) than those with essential hypertension. With primary aldosteronism, a higher aldosterone-renin ratio (odds ratio, OR = 7.85, P = 0.008) was independently related to pretreatment CysC-GFR. The factors related to pretreatment proteinuria included CysC-GFR (OR, -0.006, P = 0.001), plasma aldosterone concentration (OR, 0.004, P = 0.002), and duration of hypertension (OR, 0.016, P = 0.032). Duration of hypertension was also independently correlated with the pretreatment resistive index among primary aldosteronism patients (OR, 0.004, P = 0.035). CysC-GFR (all, P < 0.05), proteinuria (P < 0.001), and resistive index (P < 0.001) decreased 1 year after adrenalectomy but not with spironolactone treatment. CONCLUSION: Our data suggest that prolonged hyperaldosteronism will cause relative kidney hyperfiltration and reversible intrarenal vascular structural changes, which disguise the consequent renal injury, including declining GFR and proteinuria. Adrenalectomy and spironolactone treatment exert different clinical impacts toward kidney damage even with a similar blood pressure-lowering effect.

Kidney impairment in primary aldosteronism.

BACKGROUND: Kidney impairment is noted in primary aldosteronism (PA), and probably initiated by glomerular hyperfiltration. METHODS: A prospectively defined survey was conducted on 602 patients who were suspected of PA in the multiple-center Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Estimated glomerular filtration rate (eGFR) was calculated and followed up at 1 yr after treatment. RESULTS: The diagnosis of PA was confirmed in 330 patients. Among them 17% of these patients had kidney impairment (eGFR<60 ml/min/1.73 m²). Patients with PA had a higher prevalence of estimated hyperfiltration than those with essential hypertension (EH) (14.5% vs. 7.0%, p=0.005). The eGFR independently predicted PA (OR, 1.017) in the propensity-adjusted multivariate logistic model. In PA, plasma renin activity and lower serum potassium (p=0.018) was correlated with kidney impairment (p=0.001), while this relationship was not significant in patients with EH. Either unilateral adrenalectomy or treatment of spironolactone for PA patients caused a decrease of eGFR (p<0.001). Pre-operative hypokalemia (p=0.013) and the long latency of hypertension (p=0.016) could enhance the significant decrease of eGFR after adrenalectomy. CONCLUSIONS: Patients with aldosteronism had relative estimated hyperfiltration than patients with EH. Calculation of eGFR may increase the specificity in identifying patients with PA. Our findings demonstrate the correlation of serum potassium and renin with estimated hyperfiltration in PA and their relationship to kidney damage. These results provide a high priority for future renal protective strategies and methods for the early diagnosis and prompt treatment of PA.

Diagnosis of primary aldosteronism: comparison of post-captopril active renin concentration and plasma renin activity.

BACKGROUND: A common pharmacologic test for the diagnosis of primary aldosteronism (PA) is the administration of captopril to determine whether an abnormal plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio(ARR) persists, although active renin concentration (ARC) may offer advantages with regard to processing and standardization. METHODS: A prospective, head-to-head study was conducted between Feb 2008 and Dec 2008. One hundred and fourteen patients enrolled and received captopril to aid in the diagnosis of PA in the TAIPAI intervention. RESULTS: Fifty-one patients were diagnosed with PA. Post-captopril ARC was significantly correlated with PRA. The area under the receiver operating characteristic curve of the post-captopril ARR was not different in PRA vs ARC measurements. When post-captopril ARC-based ARR (ARR(ARC))>35.5 as the cut-off value, we obtained sensitivity of 75.0% and specificity of 86.4% to differentiate PA from essential hypertension. CONCLUSIONS: The correlation of individual PRA and ARC after administration of captopril was excellent; especially at the lower PRA levels. Post-captopril ARR(ARC) values used to diagnose PA are not different from post-captopril PRA-based (ARR(PRA)) values in patients without kidney, liver and heart failures. Primary aldosteronism can be diagnosed with a post-captopril cut-off value of ARR(ARC)>35.5 pmol/ng.

Association of kidney function with residual hypertension after treatment of aldosterone-producing adenoma.

BACKGROUND: Autonomous secretion of aldosterone in patients with primary aldosteronism increases glomerular filtration rate and causes kidney damage. The influence of a mild decrease in kidney function on residual hypertension after adrenalectomy is unexplored. STUDY DESIGN: Nonconcurrent prospective study. SETTING & PARTICIPANTS: The study was based on the Taiwan Primary Aldosteronism Investigation (TAIPAI) database. 150 patients (61 men; overall mean age, 47.2 +/- 11.6 years) with a diagnosis of aldosterone-producing adenoma had undergone unilateral adrenalectomy at National Taiwan University Hospital from July 1999 to January 2007. PREDICTOR: Presurgery estimated glomerular filtration rate (eGFR). OUTCOMES & MEASUREMENTS: Residual hypertension after adrenalectomy, defined either as less than 75% of recorded blood pressure measurements with systolic blood pressure less than 140 mm Hg and diastolic blood pressure less than 90 mm Hg or requiring antihypertensive medications during the first year after surgery. RESULTS: Before surgery, 27 (18%), 72 (48%), and 51 (34%) patients had moderately to severely decreased (<60 mL/min/1.73 m(2)), mildly decreased (60 or=90 mL/min/1.73 m(2)), respectively. After surgery, 16 (59.3%), 29 (40.3%), and 10 (19.3%) patients in each category had postsurgery residual hypertension. Compared with patients without decreased eGFR before surgery, adjusted odds ratios for postsurgery residual hypertension were 2.7 (95% confidence interval, 1.03 to 7.0; P = 0.04) and 2.8 (95% confidence interval, 1.05 to 9.3) for mildly and moderately to severely decreased eGFR, respectively. LIMITATIONS: Arbitrary definition for residual hypertension. CONCLUSIONS: Two-thirds of patients with aldosterone-producing adenoma were cured of hypertension by means of unilateral adrenalectomy. Kidney function impairment, even mild, appears to be associated with a high incidence of postsurgery residual hypertension.

Primary aldosteronism: diagnostic accuracy of the losartan and captopril tests.

BACKGROUND: To assess whether angiotensin-II receptor blockers (ARBs) offer any additional advantage in confirming the diagnosis of primary aldosteronism (PA) and their use in the differentiation of PA subtypes. METHODS: A prospective, cohort, head-to-head study was conducted between July 2003 and July 2006. A total of 135 patients received captopril and losartan tests to confirm the diagnosis of PA in the TAIPAI (Taiwan Primary Aldosteronism Investigation) intervention. RESULTS: In total, 71 patients were diagnosed with PA. The area under the receiver-operating characteristic (ROC) curve of the postcaptopril plasma aldosterone concentration (PAC) was significantly less than that of the postlosartan PAC (0.744 vs. 0.829, P = 0.038). Using an aldosterone-renin ratio (ARR, ng/dl per ng/ml/h) >35 with a PAC >10 ng/dl, the specificity was 89.1% vs. 93.8% and the sensitivity was 66.2% vs. 84.5 % for the captopril test vs. the losartan test, respectively. With respect to the losartan test, the accuracy was 88.9%, the agreement was good (k = 0.778), and there was no disagreement with the McNemar test (P = 0.118). Losartan had the advantage of a better negative predictive value to exclude PA when patients were referred with a serum potassium (SK) level <3.8 mmol/l. When a postlosartan ARR >60 was the cutoff value, the positive predictive value was 82% with a negative predictive value of 57% in distinguishing aldosterone-producing adenomas (APAs) from idiopathic hyperaldosteronism (IHA). CONCLUSIONS: The postlosartan ARR and PAC were shown to have better accuracy for the diagnosis of PA than the captopril test. With a postlosartan ARR >60, APAs can be adequately differentiated from IHA.

High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency.

This retrospective case-control study compared the tolerability and efficacy of linezolid between patients with and without renal insufficiency (serum creatinine > or =1.3mg/dL for women and > or =1.5mg/dL for men). All patients with Gram-positive infections treated with linezolid for more than 7 days were included. Data were collected from medical charts and differences between patients with and without renal insufficiency were analysed. Sixty-two patients (40 men), with a mean age of 56.9 years, were enrolled in this study. At the start of linezolid treatment, 17 patients (27.4%) had impaired renal function. Patients with renal insufficiency had a higher prevalence of diabetes mellitus compared with those with normal renal function (64.7% vs. 22.2%; P=0.002). At the start of therapy, patients with renal impairment had a higher frequency of elevated blood urea nitrogen (51.0+/-21.1mg/dL vs. 18.3+/-9.7mg/dL; P<0.001), elevated serum creatinine (2.3+/-0.7mg/dL vs. 0.9+/-0.3mg/dL; P<0.001) and decreased initial haemoglobin (9.2+/-1.5g/dL vs. 10.4+/-1.7g/dL; P=0.017). Development of severe thrombocytopenia (<100 x 10(9)/L) was significantly more common in patients with renal insufficiency (64.7% vs. 35.6%; P=0.039). The incidence of linezolid-associated thrombocytopenia was higher among patients with renal insufficiency. When patients with renal insufficiency are treated with linezolid for more than 2 weeks, the platelet count should be monitored at least twice a week owing to the increased likelihood of thrombocytopenia.