Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased occurrence of cardiac valve abnormalities. However, the prevalence of cardiac abnormalities in patients with a uniform genotype of ADPKD has not been previously reported. We performed M-mode and color Doppler echocardiography on 109 patients from 16 families with polycystic kidney disease type 1 (PKD1). Findings were compared with those of 73 unaffected family members and 73 healthy controls. Mitral valve prolapse was found in 26% of patients with PKD1, 14% of unaffected relatives, and 10% of control subjects. The prevalence of hemodynamically significant mitral regurgitation (grade 2 or 3) was 13%, 4%, and 3%, respectively. Prevalences of grade 2 or 3 aortic regurgitation (8%, 4%, and 3%, respectively) and tricuspid regurgitation (4%, 6%, and 7%, respectively) were not significantly different among the three groups. Left ventricular hypertrophy (LVH) was found in 19% of subjects with PKD1, 6% of unaffected relatives, and 4% of control subjects. Systolic blood pressure and severity of renal insufficiency were related to mitral regurgitation and LVH in subjects with PKD1. The prevalence of cardiac valve abnormalities did not differ between unaffected relatives and control subjects. Mitral valve prolapse is a characteristic finding in patients with PKD1. Conversely, mitral regurgitation and LVH are likely to be secondary to elevated blood pressure in these patients.

Splanchnic perfusion during hemodialysis: evidence for marginal tissue perfusion.

OBJECTIVE: Splanchnic perfusion may be compromised during hemodialysis because of hypovolemia, inflammatory response, and blood flow redistribution. The aim of this study was to assess the response of splanchnic blood flow and oxygen transport to hemodialysis. DESIGN: A prospective clinical study. SETTING: A mixed medical-surgical intensive care unit in a university hospital. PATIENTS: Nine patients with acute renal failure. INTERVENTIONS: A 4-hr period of hemodialysis. MEASUREMENTS AND MAIN RESULTS: Systemic (via a pulmonary artery catheter), hepatosplanchnic, and femoral (via dye dilution) blood flow and gastric mucosal Pco2 were measured before, during, and 2 hrs after hemodialysis. During hemodialysis, despite unchanged arterial blood pressure, cardiac output and stroke volume decreased from 3.0 +/- 1.0 L/m2/min (mean +/- sd) to 2.3 +/- 0.7 L/m2/min (p =.02), and from 38 +/- 16 mL/m2/min to 28 +/- 12 mL/m2/min (p =.01), respectively. Splanchnic but not femoral blood flow decreased from 0.9 +/- 0.3 L/m2/min to 0.7 +/- 0.2 L/m2/min (p =.02). The blood flows returned to baseline values after dialysis without need for therapeutic interventions. Gastric mucosal-arterial Pco2 gradients were high before dialysis (35 +/- 23 torr [4.6 +/- 3.1 kPa]) and did not change. Renin but not atrial natriuretic peptide concentration increased during hemodialysis from 13 +/- 13 microg/L to 35 +/- 40 microg/L and decreased afterward to baseline values (13 +/- 13 microg/L; p =.01). Whereas interleukin 6 tended to decrease, tumor necrosis factor alpha increased during hemodialysis from 74 +/- 24 pg/mL to 86 +/- 31 pg/mL and continued to increase after hemodialysis to 108 +/- 66 pg/mL (p =.022). CONCLUSION: Hemodialysis and fluid removal in normotensive patients with acute renal failure may result in a reduction of systemic and splanchnic blood flow that is undetectable using traditional clinical signs. In contrast to what is observed in hypovolemia, the changes in regional blood flow are rapidly reversible after hemodialysis.

Brachial arterial access: endovascular treatment of failing Brescia-Cimino hemodialysis fistulas--initial success and long-term results.

PURPOSE: To evaluate safety and efficacy of endovascular interventions in failing antebrachial Brescia-Cimino hemodialysis fistulas in consecutive patients. MATERIALS AND METHODS: Altogether, 103 interventions were performed in 53 Brescia-Cimino shunts in 51 patients by means of antegrade brachial arterial access. Twelve interventions were initiated with pharmacomechanical thrombolysis and/or thromboaspiration. All interventions included balloon angioplasty that was completed with stent placement in eight cases and with endovascular brachytherapy with an iridium 192 source in five cases. RESULTS: The technical success rate of the primary interventions was 92% (49 of 53) and that for all interventions was 95% (98 of 103). The rate of major complications was 4% (four of 103). Clinical success was achieved in 92% (95 of 103) of the interventions. By including the initial failures, 58% +/- 7 (standard error of the estimate), 44% +/- 8, 40% +/- 8, and 32% +/- 10 primary and 90% +/- 5, 85% +/- 5, 79% +/- 7, and 79% +/- 7 secondary clinical patency rates were registered at 6 months and 1, 2, and 3 years, respectively, by means of Kaplan-Meier analysis. The location of the main treated lesion at the arteriovenous anastomosis (P =.03) was a predictor of poorer long-term patency. CONCLUSION: Endovascular interventions with antegrade brachial arterial access are highly effective in restoring function in failing Brescia-Cimino fistulas.

Intensive treatment of rheumatoid arthritis reduces need for dialysis due to secondary amyloidosis.

We have analysed changes in the intensity of treatment of patients with rheumatoid arthritis (RA) and its influence on the number of patients with RA and secondary amyloidosis (SA) admitted to dialysis due to end-stage renal disease. The number of visits and patients at the rheumatological outpatient clinic because of RA, the type of medication used in 1988-1997, and the number of patients with RA and SA on dialysis from 1989 to 1999 were extracted from the data set of Kuopio University Hospital. The intensity of treatment could be evaluated as the treated number of patients with RA and the number of visits at the outpatient clinic. Both the numbers increased from 1988 to 1996, patients under treatment from 201 to 550 and visits from 1091 to 2198, respectively. In 1997, the number of patients still increased (n=637), although the number of visits started to decline (n=2054), partly due to better collaboration of health centres. A marked shift from use of only symptomatic treatment or one disease-modifying antirheumatic drug (DMARD) to more common use of immunosuppressants and/or combinations of at least two DMARDs occurred in the five years from 1992 to 1997. In 1988, the figures for only nonsteroidal anti-inflammatory drugs or only glucocorticoids or one immunosuppressive drug were 24%, 8%, and 9%, and in 1997, 4%, 3%, and 22%, respectively. In 1997, 43% of the patients were treated with combinations of two or more DMARDs. The number of patients with RA on dialysis treatment and the number of new admissions each year due to SA decreased from 11 to 2 and from 5 to none, respectively. At the beginning of year 2000 there was only one patient with RA and SA on dialysis.

Which anti-hypertensive to add to a beta-blocker: ACE inhibitor or diuretic?

Thirty-eight patients already treated with atenolol 50 mg once daily were randomly assigned to treatment with either hydrochlorothiazide (12.5-25 mg once daily) or lisinopril (10-20 mg once daily) for 8 weeks in a double-blind crossover study. Eight weeks' treatment with the combination of ACE inhibitor and beta-blocker or the diuretic and beta-blocker produced falls in blood pressure (lying: -8.4 +/- 15.4/ -7.3 +/- 80 mmHg and -6.1 +/- 15.3/ -5.2 +/- 8.8 mmHg [mean +/- SD] for lisinopril and hydrochlorothiazide respectively; standing: -10.2 +/- 14.2/8.2 +/- 9.2 mmHg and -6.8 +/- 14/ -6.3 +/- 10.3 mmHg for lisinopril and hydrochlorothiazide respectively) which were not statistically significantly different. Heart rate was significantly increased on the combination of beta-blocker and diuretic (lying: +4.3 +/- 10.7; standing: +3.2 +/- 10.0 beats/min) compared with a fall on beta-blocker+ACE inhibitor (lying; -0.5 +/- 7.6; standing: -1.5 +/- 7.4). Both therapeutic regimens were equally well tolerated. These results suggest that where patients fail to respond to monotherapy with a beta-blocker the addition of an ACE inhibitor may be as effective as the more traditional option of diuretic therapy.

Relationship of branched-chain alpha-keto-acids and lipids in sera of hypertriglyceridemic subjects.

According to the present study, in hyperlipidemias where triglyceride values in serum are raised, the triglyceride values are associated with increased amounts of branched-chain alpha-keto-acids (BCKA) in the serum. In particular, the concentration of alpha-ketoisocaproic acid (KICA), which in the control sera was 34.4 mumol/l, was in type IIB hyperlipidemia 40.4% and in type IV 49.4% higher than in controls with normal serum lipid values. In type IV hyperlipidemia, values for alpha-ketoisovaleric acid (KIVA) and alpha-keto-beta-methyl-n-valeric acid (KMVA) were also high when compared to the corresponding mean values of the controls, 7.1 and 18.8 mumol/l. The respective differences were 57.7 and 44.1 per cent. In type IIB hyperlipidemia, KIVA was significantly and KMVA insignificantly increased compared to the control group. In type IIA hyperlipidemia with normal triglyceride values, none of the three BCKA differed significantly from the controls. These results also indicate that the increased amounts of individual BCKA somehow depend on the concentration of triglycerides in serum, while no relationship was found between BCKA values and cholesterol concentration.

Localisation of a mutation producing autosomal dominant polycystic kidney disease without renal failure.

A four generation Finnish family was identified with atypical features of adult polycystic kidney disease. All members of the extended pedigree were asymptomatic and none had developed renal failure. Previous studies have shown close linkage between the adult polycystic kidney disease locus and the alpha chain of human haemoglobin on chromosome 16, but these studies were carried out on families manifesting 'typical' clinical features of the disease. In order to determine whether the atypical clinical features observed in this Finnish family were produced by a mutation at the same or a second locus, linkage studies were carried out using a highly polymorphic DNA marker from the alpha globin cluster. Here we show that the mutation producing the disease in this Finnish family is also closely linked to alpha globin.

The value of scintigraphy and computed tomography for the differential diagnosis of primary hyperaldosteronism.

Adrenocortical adenoma is the most common cause of primary hyperaldosteronism. Most tumours are small, less than 2 cm in diameter and, therefore, their localization may be difficult. We have compared two different methods, adrenal scintigraphy (AS) and computed tomography (CT) in the differential diagnosis of 12 patients with primary hyperaldosteronism. AS was performed using either [131I]cholesterol or 6-iodomethyl-19-norcholesterol during dexamethasone suppression. Of the patients, five showed a normal CT and symmetrical uptake of the isotope as AS. They were considered representative of bilateral hyperplasia. All showed good therapeutic response to spironolactone. Seven patients had an adrenocortical adenoma verified at operation. The CT finding indicated a tumour in five patients. This was correct in four, but in one patient the adenoma was found in the contralateral adrenal gland. In two patients with an adenoma, CT was considered normal. AS correctly indicated the tumour in all seven patients. The uptake was unilateral in six, and bilateral but clearly asymmetrical in one patient. The results indicate that AS is superior to CT in the pre-operative localization of aldosteroma. Although CT remains the primary method for the investigation of these patients, AS should be applied always when CT does not unequivocally indicate the presence and localization of an adrenal tumour.

Is air under the diaphragm a significant finding in CAPD patients?

The incidence of air under the diaphragm in CAPD patients is very low, and causes directly attributable to standard CAPD techniques are even lower. Bowel perforation generally causes a larger volume of air collection under the diaphragm.

Bumetanide kinetics in renal failure.

To study the effects of renal failure on bumetanide kinetics, we administered single intravenous doses of 1.0 mg/3.08 microCi 14C-bumetanide to six healthy subjects and 22 patients with variable degrees of renal failure. The kinetics of 14C-bumetanide and total 14C were adequately described by a two-compartment open model in the control subjects and in the patients. The volume of the central compartment and the distribution t1/2 were of the same order in both groups, whereas the mean (+/- SE) volume at steady state was larger (22.1 +/- 1.6 and 16.9 +/- 1.0 L) and the elimination t1/2 was longer (1.9 +/- 0.2 and 1.4 +/- 0.1 hours) in patients with renal failure than in healthy controls. Bumetanide renal clearance was lower (10 +/- 3 and 90 +/- 13 ml/min) in patients than in subjects and correlated with creatinine clearance (r = 0.784) and log serum creatinine level (r = -0.843), whereas nonrenal clearance was significantly higher in the patients (153 +/- 14 and 99 +/- 6 ml/min). Bumetanide total plasma clearance did not significantly change. The non-protein-bound, free fraction of bumetanide was higher in patients and correlated with plasma albumin levels (r = -0.777). The kinetics of total 14C showed similar but greater changes than those of 14C-bumetanide. Thus the most important changes in bumetanide kinetics in patients with renal failure are low renal clearance and a high free fraction, with a consequent increase in nonrenal clearance, volume of distribution, and elimination t1/2.

The neutrophil function of uremic patients treated by hemodialysis or CAPD.

The phagocytic, bactericidal and chemotactic function of blood neutrophils in uremic patients treated either by CAPD or hemodialysis was assessed in vitro. The phagocytosis was normal in 11 patients on CAPD treatment while it was significantly impaired in 13 patients on maintenance hemodialysis (HD) treatment. In addition the chemotactic function of neutrophils seemed to be better on CAPD treatment, when heat-inactivated serum, zymosan or casein were used as chemoattractants, but the difference was significant only with heat-inactivated serum. In contrast the chemotactic response to Staphylococcus aureus was better in patients on HD treatment. The intracellular killing of bacteria was normal in both patient groups. The more stable metabolic control of acid-base and electrolyte balance and the better clearance of middle molecules could explain the better performance of uremic neutrophils in the patients on CAPD treatment.