[Interview with Vito Cagli: his life as a nephrologist and more].

This interview describes the numerous and important contributions that Vito Cagli, who was born in Ancona in 1926, has given to the Italian Nephrology and to other fields of Medicine. These contributions, that are very poorly known today, were produced especially in the years in which Cagli worked as deputy director of the Centre for the Investigation and Treatment of Hypertension and Renal Diseases at Policlinico Hospital Umberto I in Rome. This interview also describes the early phase of Italian Nephrology before the introduction in our country of renal biopsy and of hemodialysis.

Association of reduced kidney function with cardiovascular disease and mortality in elderly patients: comparison between the new Berlin initiative study (BIS1) and the MDRD study equations.

BACKGROUND: New creatinine based equations for estimating glomerular proposed for aged subjects have not been assessed in their association of reduced eGFR with cardiovascular (CV) morbidity or all cause (AC) mortality. PATIENTS: All subjects ≥70 years old (2998) who had been admitted to the hospital during a 12 month period were examined. METHODS: In a cohort study we applied the new Berlin Initiative Study (BIS1) equation. We compared the association of reduced eGFR estimated by BIS1 and MDRD equations, with cardiovascular (CV) disease and all cause (AC) mortality. RESULTS: eGFR was 57 ± 17 mL/min/1.73 m2 by MDRD and 71 ± 28 mL/min/1.73 m2 by BIS1 (P < 0.001). A diagnosis of CV disease was present in 947 patients. CV disease was associated with eGFR < 60 mL/min/1.73 m2 by both formulas: OR 1.179 (CI 1.001-1.390) for BIS1 and OR 1.440 (CI 1.223-1.696) for MDRD. In survival analysis a significant association of eGFR < 60 mL/min/1.73 m2 with AC mortality was found for both equations: MDRD (HR = 1.270, CI 1.111-1.453, P < 0.001), BIS1 (HR = 1.174, CI 1.031-1.338, P = 0.016). The analysis repeated with groups of age showed that the association of mortality with eGFRBIS1 < 60 mL/min/1.73 m2 was lost over 80 years. CONCLUSIONS: In patients >70, admitted to hospital, the implementation of the new BIS1 estimating equation does not modify the relationship, observed with the MDRD formula, of reduced GFR with CV disease or AC mortality.

Combined pulmonary hypertension and renal thrombotic microangiopathy in cobalamin C deficiency.

Pulmonary arterial hypertension (PAH) and renal thrombotic microangiopathy (rTMA) are rare diseases in childhood, frequently leading to death and end-stage renal disease, respectively. Their combined occurrence has been reported anecdotally. We investigated the clinical, biochemical, and genetic aspects of 5 children with the rare combination of PAH and rTMA. Onset of disease ranged from 1.5 to 14 years of age. The 2 youngest patients presented with concomitant pulmonary and renal disease; in the older patients, PAH was preceded by rTMA from age 2.5 to 7 years. Three patients presenting at ≤ 3 years of age died of right ventricular failure secondary to progressive PAH. In 2 patients, cobalamin C (cblC) deficiency was diagnosed postmortem. Three patients were treated with hydroxocobalamin; 1 died 2 weeks after diagnosis, 1 patient exhibited progressive pulmonary vasculopathy, and 1 patient is currently in stable condition. cblC deficiency was diagnosed biochemically 2 days to 18 years after initial presentation. Genetic analysis confirmed mutations in MMACHC in all patients; 4 patients were compound heterozygous, with all having base-pair substitutions (G>A or G>T) at nucleotide 276 in addition to frame-shift mutations. One patient had homozygous nonsense mutations of MMACHC. We established cblC deficiency as the denominator in the rare combination of PAH and rTMA in these children. Early recognition of cblC deficiency and vigorous treatment with hydroxocobalamin may beneficially affect the course of this devastating disease.

Thrombotic microangiopathic nephropathy, pulmonary hypertension and nephromegaly: case report of a patient treated with endothelin receptor antagonist.

The coexistence of thrombotic microangiopathic nephropathy and pulmonary hypertension has only been described in association with malignancy and its treatment. Here we describe a 14-year-old boy with no prior medical history who presented with hypertension, proteinuria and nephromegaly, and then developed progressive pulmonary hypertension. Renal histology showed lesions consistent with glomerulopathy due to thrombotic microangiopathy (TMA). Pulmonary hypertension was controlled by the use of an oral endothelin receptor antagonist (bosentan). Although renal function deteriorated at the onset of pulmonary hypertension, an improvement was observed after the bosentan treatment. Nephromegaly persisted, but current creatinine clearance values are within the normal range. While this case exemplifies how thrombotic microangiopathic nephropathy may be associated with pulmonary hypertension, a therapeutic role of endothelin antagonists is suggested, not only for pulmonary hypertension but also for microangiopathic nephropathy.

Resistant arterial hypertension: association with syncronous kidney cancer and adrenal adenoma.

The coexistence of renal cancer and adrenal adenoma is rare. We report the case of a 60-year-old patient with synchronous hypernephroma and adrenal adenoma. The patient presented with resistant hypertension, high plasma renin activity and aldosterone and target organ damage. Removal of the affected kidney cured the hypertension and normalized the plasma renin activity (PRA) and circulating aldosterone. This suggests that the coexistence of kidney cancer and adrenal adenoma may be a curable cause of resistant hypertension. The potential mechanisms accounting for the lack of suppression of PRA are discussed.

Association of interleukin-6 -174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients.

BACKGROUND: Gene polymorphisms of proinflammatory cytokines, such as interleukin-6 (IL-6) and the chemokine receptor CX3CR1, have been found in association with cardiovascular disease in the general population. In dialysis patients, in whom the prevalence of cardiovascular comorbidity is strikingly high, these polymorphisms have not been investigated. METHODS: The -174G/C polymorphism of the IL-6 gene and the chemokine receptor CX3CR1 polymorphisms 249V/I and 280T/M were examined for their association with cardiovascular abnormalities in a cohort of 161 patients with end-stage renal disease (ESRD) treated by hemodialysis. Arterial blood pressure, electrocardiogram (ECG) ischemic changes, and left ventricular mass index (LVMI) were the parameters examined for the association study. The control group was made up of 169 healthy subjects. RESULTS: We found that for both IL-6 and chemokine receptor, genotype frequency and allelic distribution in both ESRD patients and controls were comparable. The genetic association study showed that in the whole group of dialysis patients, individuals with GC + CC genotype for the -174G/C polymorphism had a higher diastolic blood pressure (P = 0.008) and LVMI (P = 0.026) than GG homozygotes. The prevalence of left ventricular hypertrophy (LVH) in the former group was 58.6% vs. 39.2% in the latter (P = 0.02). The same analysis limited to diabetic patients in dialysis, showed that the prevalence of LVH in those with CG + CC genotype was 87.5% vs. 36.3% in those with GG genotype (P = 0.02). In diabetic patients, lower levels of serum albumin was found in the GC + CC genotypic group than in GG subjects; 34.63 +/- 5.18 g/L vs. 41.75 +/- 4.79 g/L (P = 0.003). CONCLUSION: These data demonstrate an association between the IL-6 promoter polymorphism -174G/C and high blood pressure and LVH in hemodialysis patients, especially those with diabetes. The results strengthen the hypothesis that chronic inflammation is a mechanism of cardiovascular damage in dialysis patients and the role played by the IL-6 system in this mechanism.