Renjiro Kuriyama

High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

BackgroundMetabolic acidosis leads to chronic kidney disease (CKD) progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression.MethodsOne hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR) or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome.ResultsFemale patients were 36.3%: average age (SD), 70.4 (6.6) years; eGFR, 25.7 (13.6) ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2) mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8) mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3) mEq/l]: adjusted hazard ratio (HR), 3.511 (95% CI, 1.342-9.186). A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI), 0.684-0.914].ConclusionsIn elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression.

Dietary Acid Intake and Kidney Disease Progression in the Elderly

Background/Aims: Non-volatile acid is produced by metabolism of organic sulfur in dietary protein, and promotes kidney damage. We investigated the role of dietary acid load, in terms of net endogenous acid production (NEAP), in chronic kidney disease (CKD) progression. Methods: 217 CKD patients on low-protein diet with a normal serum bicarbonate level were enrolled in this retrospective cohort study in Japan. The primary outcome was 25% decline in estimated glomerular filtration rate (eGFR) or start of dialysis. Their NEAP was measured every 3 months. The patients were categorized into four groups on the basis of quartiles of NEAP every 3 months. The groups were treated as time-dependent variables. Results: The average age (SD) was 70.6 (7.1) years; eGFR 23.5 (14.2) ml/min/1.73 m2. Analysis using extended Cox models for the NEAP groups adjusted for baseline characteristics (referring to group 1 showing the lowest NEAP) showed that high NEAP was associated with a high risk of CKD progression; group 2, adjusted hazard ratio (HR) 3.930 (95% confidence interval (CI) 1.914, 8.072); group 3, adjusted HR 4.740 (95% CI 2.196, 10.288); group 4, adjusted HR 4.303 (95% CI 2.103, 8.805). Logistic regression analysis adjusted for baseline characteristics showed that the occurrence of hypoalbuminemia or hyperkalemia was associated with low serum bicarbonate level and the presence of complications at baseline, but not with NEAP. Conclusion: In elderly CKD patients, our findings suggest that high NEAP is independently associated with CKD progression. The decrease in NEAP may be an effective kidney-protective therapy.

Effect of thrombocytopenia on the onset of immune complex glomerulonephritis

The effect of platelets on the development of immune complex glomerulonephritis (GN) was examined using bovine serum albumin (BSA) GN with platelet depletion. To clarify the role of platelets in the initial stage of BSA GN, thrombocytopenia was induced before BSA infusion. In 18 New Zealand white rabbits, BSA was intravenously injected twice after the presensitization. Eight of these BSA GN rabbits were injected daily with goat anti-rabbit platelet antiserum to induce thrombocytopenia, and platelet counts were maintained below 5 x 10(4)/microliters throughout the experiment. In the thrombocytopenic group, the degree of proteinuria was significantly decreased compared to the control group. Glomerular polymorphonuclear leukocyte infiltration, mononuclear cell proliferation, exudation and glomerular enlargement were significantly suppressed in the thrombocytopenic group. The results suggest that platelets may be quite important in the initiation and development of immune complex GN.

Intermittent high-dose oral 1,25-dihydroxyvitaimin D3 for secondary hyperparathyroidism in hemodialysis patients

AbstractWe attempted to confirm whether intermittent high-dose oral 1,25-dihydroxyvitamin D3 (PULSE) suppressed parathyroid hormone (PTH) secretion, inhibited parathyroid cell proliferation, and increased bone mass in uremic patients (Pts). Twenty two long-term hemodialysis Pts with secondary hyperparathyroidism were given 3.4±0.8µg 1,25 dihydroxyvitamin D3 twice a week for 9.5±3.3 M. The size of parathyroid gland (PT) was estimated by echography and computed tomography every 3 months. Bone mineral density of the radius (BAD) was measured by single photon absorptiometer (Norland SPA 26).Findings were:-Before PULSE6 monthsP-valueCa (mg/dl)9.96± 1.1811.15± 1.61<0.001P (mg/dl)5.17± 1.835.78 ± 1.11n.s.Alk-Pase (IU)373 ± 385167± 79<0.005HS-PTH (ng/ml)49.9±31.58.01±3.83<0.005I-PTH (pg/ml)563± 453165 ± 101<0.005 The volumes of 22 PT detected by echography in 11 Pts before and after PULSE were 363±385 and 434±462cmm (n.s.), respectively. In 6 Pts before the PULSE therapy began and after 11.OM of PULSE, The BAD values were measured in 6 Pts before and after 11.OM of PULSE. They were 0.388±0.115 and 0.398±0.093 g/cm2 (n.s.), respectively.We conclude that at this dose schedule, PULSE suppresses PTH secretion, but does not decrease PT size or increase the bone mass.