sodium-bicarbonate and Albuminuria

In most patients with hypertensive nephropathy and low glomerular filtration rate (GFR), the kidney function progressively declines despite the adequate control of the hypertension with angiotensin-converting enzyme inhibition. Previously we found that 2 years of oral sodium citrate slowed GFR decline in patients whose estimated GFR (eGFR) was very low (mean 33 ml/min). This treatment also slowed GFR decline in an animal model of surgically reduced nephron mass. Here, we tested if daily oral sodium bicarbonate slowed GFR decline in patients with hypertensive nephropathy with reduced but relatively preserved eGFR (mean 75 ml/min) in a 5-year, prospective, randomized, placebo-controlled, and blinded interventional study. Patients matched for age, ethnicity, albuminuria, and eGFR received daily placebo or equimolar sodium chloride or bicarbonate while maintaining antihypertensive regimens (including angiotensin-converting enzyme inhibition) aiming for their recommended blood pressure targets. After 5 years, the rate of eGFR decline, estimated using plasma cystatin C, was slower and eGFR was higher in patients given sodium bicarbonate than in those given placebo or sodium chloride. Thus, our study shows that in hypertensive nephropathy, daily sodium bicarbonate is an effective kidney protective adjunct to blood pressure control along with angiotensin-converting enzyme inhibition.

Topics: Administration, Oral; Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Cystatin C; Double-Blind Method; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Kidney Diseases; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Sodium Bicarbonate

The aim of this study is to investigate the effect of sodium bicarbonate on doxorubicin-injected rats. Thirty female Wistar rats were injected with doxorubicin (3.5 mg/kg of body weight, intravenously) and 30 rats with 0.15 mol/L of sodium chloride solution (group C). Fifteen days later, we replaced the drinking water with a 0.15-mol/L sodium bicarbonate solution for 10 of the animals injected with doxorubicin (group AD-B). Three months after the beginning of treatment, urine samples were collected to quantify albumin, creatinine, and transforming growth factor-beta (TGF-beta). The rats were killed, and the kidneys were removed for histological, morphometric, immunohistochemical, and RNA studies. All doxorubicin-injected animals showed structural renal changes. However, these alterations were less intense in rats treated with doxorubicin plus sodium bicarbonate (P < 0.05). The percentage of glomerulosclerosis was 0.11% +/- 0.08% in group C, 14.7% +/- 12.8% in group AD (rats treated with doxorubicin only), and 4.38% +/- 1.9% in group AD-B, and the percentage of tubulointerstitial damage was 0. 01% +/- 0.03% in group C, 54.6% +/- 20.3% in group AD, and 16.6% +/- 10.3% in group AD-B. The immunostaining for TGF-beta in the renal cortex and glomeruli was more intense in the animals injected with doxorubicin only. A greater renal cortical TGF-beta messenger RNA content was observed in the animals injected with only doxorubicin that did not receive sodium bicarbonate (P < 0.05). These animals also presented a greater rate of urinary TGF-beta excretion reported as picograms of TGF-beta per milligram of urinary creatinine (P < 0.05), which was 202 +/- 11 pg/mg in group C, 1, 103 +/- 580 pg/mg in group AD, and 299 +/- 128 pg/mg in group AD-B. However, albuminuria was more intense in the sodium bicarbonate-treated animals (P < 0.05). The animals from group AD also showed higher immunostaining scores for vimentin and albumin in tubule cells (P < 0.05). In conclusion, treatment with sodium bicarbonate reduces structural renal damage, albumin reabsorption, and renal TGF-beta production in rats with doxorubicin-induced nephropathy.

Topics: Albumins; Albuminuria; Animals; Doxorubicin; Female; Fibronectins; Immunohistochemistry; Kidney; Kidney Diseases; Rats; Rats, Wistar; Serum Albumin; Sodium Bicarbonate; Transforming Growth Factor beta; Vimentin

Infusion of an acidic amino acid, L-aspartate, to 10 volunteers resulted in transient, significant increases in urinary excretion of the major urinary trypsin inhibitor (p less than 0.002) and beta 2-microglobulin (p less than 0.02). Simultaneously with the proteinuria, urinary pH rose significantly (p less than 0.02). These changes appeared following the infusion and after the excretion of L-aspartate had reached the preinfusion level. Albumin excretion was unchanged indicating that the proteinuria was due to a decreased tubular reabsorption. The mechanism for the reversible tubular proteinuria is unknown. A simple pH effect due to alkalization of the urine was excluded, as NaHCO3 infusion was not followed by an increase in the excretion of the major urinary trypsin inhibitor and beta 2-microglobulin.

Topics: Adult; Albuminuria; Arginine; Aspartic Acid; beta 2-Microglobulin; Bicarbonates; Female; Glycoproteins; Humans; Infusions, Intravenous; Kidney Tubules, Proximal; Male; Proteinuria; Sodium; Sodium Bicarbonate

The albuminuria occurring after swimming in splenectomized dogs was investigated. Swimming in splenectomized dogs induces metabolic acidosis, a decrease in renal vascular conductance, and an increase in plasma renin activity, all three factors possibly implicated in the occurrence of albuminuria. The administration of sodium bicarbonate prior to swimming reduced the magnitude of the acidosis and eliminated the increase in albuminuria after swimming. Phenoxybenzamine, an alpha-adrenergic blocking agent that maintains the renal blood flow during exercise also blocked the increase in albuminuria despite a decrease of blood pH during swimming. However, after metoprolol, a beta 1-adrenergic blocking agent that blocks the rise in plasma renin activity during exercise, swimming causes a threefold increase in albuminuria (P less than 0.01). The albuminuric response to swimming preceded by saline was also significant (P less than 0.05). It is likely that post-swimming albuminuria in splenectomized dogs is linked to the decrease of renal vascular conductance or to the decrease in blood pH rather than to the rise in plasma renin activity.

Topics: Acidosis; Albuminuria; Animals; Bicarbonates; Blood; Dogs; Hydrogen-Ion Concentration; Metoprolol; Muramidase; Phenoxybenzamine; Renal Circulation; Renin; Sodium Bicarbonate; Splenectomy; Swimming

40-mg doses of human cationic (CA) or anionic (AA) albumin were administered intravenously to 48 normal female rats. Sodium bicarbonate (NaHCO3) was administered to 8 of these animals before CA or AA. Urine alkalinization caused increased renal CA excretion in CA-injected animals, which also showed marked reduction of the intensity of the renal changes produced by CA.

Topics: Albumins; Albuminuria; Animals; Bicarbonates; Cations; Female; Hydrogen-Ion Concentration; Kidney Tubules, Proximal; Rats; Rats, Inbred Strains; Sodium Bicarbonate; Urine