The relationship between gut dysbiosis and obesity is currently acknowledged to be a health topic which causes low-grade systemic inflammation and insulin resistance and may damage the kidney. Organic anion transporter 3 (Oat3) has been shown as a transporter responsible for renal handling of gut microbiota products which are involved in the progression of metabolic disorder. The present study investigated the effect of probiotic supplementation on kidney function, renal Oat3 function, inflammation, endoplasmic reticulum (ER) stress, and apoptosis in obese, insulin-resistant rats. After 12 weeks of being provided with either a normal or a high-fat diet (HF), rats were divided into normal diet (ND); ND treated with probiotics (NDL); HF; and HF treated with probiotic (HFL). Lactobacillus paracasei HII01 1 × 10 8 colony forming unit (CFU)/ml was administered to the rats daily by oral gavage for 12 weeks. Obese rats showed significant increases in serum lipopolysaccharide (LPS), plasma lipid profiles, and insulin resistance. Renal Oat 3 function was decreased along with kidney dysfunction in HF-fed rats. Obese rats also demonstrated the increases in inflammation, ER stress, apoptosis, and gluconeogenesis in the kidneys. These alterations were improved by Lactobacillus paracasei HII01 treatment. In conclusion, probiotic supplementation alleviated kidney inflammation, ER stress, and apoptosis, leading to improved kidney function and renal Oat3 function in obese rats. These benefits involve the attenuation of hyperlipidemia, systemic inflammation, and insulin resistance. The present study also suggested the idea of remote sensing and signaling system between gut and kidney by which probiotic might facilitate renal handling of gut microbiota products through the improvement of Oat3 function.

Patients with OSAS (obstructive sleep apnoea syndrome) demonstrate renal signs such as proteinuria, glomerular hypertrophy and focal glomerular sclerosis. We performed a clinical study to investigate the glomerular function in OSAS patients and the short-term effect of CPAP (continuous positive airway pressure) on it. OSAS patients underwent a sodium thiosulphate and p -aminohippurate double clearance test, polysomnography and ambulatory blood pressure monitoring before and a week after the induction of CPAP. Twenty-seven consecutive patients (24 males) with moderate-to-severe OSAS admitted to our hospital for the induction of CPAP, and 32 healthy donors for renal transplantation as controls participated in the study. Before treatment, the glomerular filtration rate, estimated by the sodium thiosulphate clearance test, was within normal range, and the renal plasma flow was significantly lower than normal in the OSAS patients, thus the FF (filtration fraction) value was much higher than normal. FF before CPAP was not significantly correlated with age, body mass index or blood pressure; however, indices of increased hypoxaemia correlated with increased FF values. Polysomnographic variables after CPAP showed significant improvements in all patients, and only the nocturnal blood pressures were slightly lower than before CPAP. In 21 patients who underwent the clearance test after CPAP, FF significantly decreased from 0.26±0.04 to 0.23±0.03 ( P <0.001). OSAS patients were generally in a glomerular-hyperfiltrating condition that appeared to cause the renal findings associated with OSAS. CPAP might prevent nephropathy by ameliorating the glomerular hyperfiltration in OSAS patients.

The present study investigated the potential role of nitric oxide (NO) and its interaction with renal sympathetic nerves in modulating the excretory responses to an acute saline volume expansion (VE), of 10% of body weight, in the innervated and denervated kidneys of both lean and obese Zucker rats. This was done using the NO synthase inhibitors N G -nitro- l -arginine methyl ester ( l -NAME), 7-nitroindazole and aminoguanidine. In lean rats, cumulative urinary sodium excretion (cu U Na V ) after 40 min of VE in the innervated kidney was enhanced by 48% in l -NAME-treated rats compared with that in untreated rats, but this was not the case for the denervated kidney. VE in untreated obese rats raised cu U Na V to a lesser extent than in the untreated lean rats, by 36% and 46% in the denervated and innervated kidneys respectively (both P < 0.001). l -NAME treatment of obese rats increased cu U Na V after VE compared with that in untreated obese rats, by 48% in the denervated kidney and by 136% in the innervated kidney (both P < 0.001). The magnitude of cu U Na V after VE in both kidneys of 7-nitroindazole-treated obese rats was not different from that in untreated obese rats. However, cu U Na V was raised ( P < 0.01) by 56% in the innervated, but not the denervated, kidney of aminoguanidine-treated obese rats. These data show that NO is partially involved in mediating the reflex renal responses to VE in Zucker rat strains. NO, possibly generated by endothelial NO synthase, exerts its effects in obese rats through a renal-nerve-independent mechanism, while the effect of NO generated by inducible NO synthase requires intact renal innervation.

1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance ( C Li ) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo or 450 mg or 600 mg of lithium given in random order at 22.00 hours. After an overnight fast, renal clearance studies were performed during a 1 h baseline period and subsequently during the second hour of an infusion of 3 μg min −1 kg −1 of dopamine. 2. Baseline values of endogenous C Li and fractional excretion of lithium (FE Li ) [27.0 (23.5–30.5) ml/min and 24.2 (203–28.2)% (means with 95% confidence interval)] were lower than exogenous values [lithium, 450 mg: 32.7 (29.9–35.4) ml/min ( P < 0.05) and 27.4 (25.2–29.6)% ( P < 0.05); lithium, 600 mg: 33.4 (29.2–37.6) ml/min ( P < 0.05) and 28.6 (26.3–31.0)% ( P < 0.01)]. Both test doses of lithium increased the baseline sodium clearance ( C Na ), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased C Na to similar values on the three study days. C Li increased to 40.9 (35.5–46.5) ml/min (endogenous lithium, P < 0.001), 43.2 (40.8–45.6) ml/min (450 mg of lithium, P < 0.01) and 44.9 (41.3–48.4) ml/min (600 mg of lithium, P < 0.001), respectively. FE Li increased to 32.2 (27.5–37.0)% ( P < 0.01), 35.4 (33.0–37.7)% ( P < 0.01) and 35.9 (32.8–38.9)% ( P < 0.01), respectively. Values during dopamine infusion did not differ significantly. 4. The lower baseline values of endogenous C Li and FE Li compared with exogenous values suggest that C Li in humans depends on the plasma concentrations of lithium. However, the effect of dopamine on C Li and FE Li was expressed to the same extent with endogenous and exogenous lithium, indicating that the two methods are interchangeable for estimation of dopamine-induced changes in tubular function.

1. In order to investigate the modulation of kidney function in insulin-dependent diabetes mellitus, intra-individual variation in glomerular filtration rate, renal plasma flow, urinary albumin excretion rate and mean arterial blood pressure was assessed in 22 normoalbuminuric patients [age 31 ± 8 years, duration of diabetes 9 ± 5 years, mean arterial blood pressure 90 ± 5 mmHg (means ± sd ), urinary albumin excretion rate 5.4 × / ÷ 1.6 μg/min]. The variation in these parameters was calculated from the results of two clearance studies (continuous infusion of [ 125 I]-iothalamate and 131 I-hippuran as markers for glomerular filtration rate and renal plasma flow, respectively) and was subsequently analysed in relation to individual variation in plasma concentrations of atrial natriuretic peptide, arginine vasopressin, angiotensin II and aldosterone and measures of glycaemic control. 2. Simple correlation analysis showed a significant association between intra-individual variation in glomerular filtration rate and atrial natriuretic peptide (σ = 0.66, P = 0.003). Besides variation in atrial natriuretic peptide, multiple regression analysis identified variation in glycated haemoglobin (P = 0.026) and arginine vasopressin (P = 0.057) as variables having independent association with variation in glomerular filtration rate [ R 2 with the three variables included (adjusted for degrees of freedom) = 0.50, analysis of variance: P = 0.002]. 3. With respect to variation in renal plasma flow, differences in fasting blood glucose concentration and mean arterial blood pressure were suggested as determinants ( R 2 = 0.36, analysis of variance: P = 0.009). 4. Variation in urinary albumin excretion rate (after log transformation) was statistically associated with variation in glycated haemoglobin. 5. When compared with eight healthy control subjects, atrial natriuretic peptide was moderately increased in the diabetic patients [4.7(4.2–6.2) versus 3.9 (3.4–4.6) pmol/l, median (first and third quartile), 2 P <0.05]. 6. In conclusion, the study identified individual changes in atrial natriuretic peptide, arginine vasopressin and long-term glycaemic control as factors associated with intra-individual variation in glomerular filtration rate. It is suggested that atrial natriuretic peptide is involved in the regulation of glomerular filtration rate and possibly specifically in diabetic hyperfiltration.

1. Previous studies have indicated that increases in dietary K + promote diuresis and retard stroke development in stroke-prone spontaneously hypertensive rats (spSHR) fed a Japanese-style diet containing 4% NaCl. 2. It is possible that elevations in dietary K + retard stroke development by inducing natriuresis and facilitating the clearance of Na + , and that diuretics associated with natriuresis might also be capable of retarding stroke development in spSHR. To test if this was the case, the onset of stroke development in spSHR fed a low (0.75%) K + diet containing 4% NaCl (controls) was monitored and compared with that in spSHR treated with (a) frusemide, (b) chlorothiazide, (c) amiloride or (d) acetazolamide, and with (e) untreated spSHR fed a high (2.11%) K + diet. 3. The onset of stroke, as well as death resulting from stroke, occurred at a significantly later age in spSHR fed a high K + diet than in spSHR fed a low-K + diet, despite the fact that both groups of spSHR rats had comparable blood pressures. 4. Treatment of spSHR with the above-named diuretics before stroke development did not alter the blood pressure of the rats. The onset of stroke development and death in spSHR treated with chlorothiazide, amiloride or acetazolamide was comparable with that observed in untreated control spSHR. In spSHR treated with frusemide, the onset of stroke was comparable with that of untreated control spSHR, whereas the onset of death after stroke development was accelerated. 5. Post mortems performed on spSHR that developed stroke indicated the presence of haemorrhagic stroke of comparable severity in the six groups of spSHR studied. 6. The results indicate that treatment of spSHR with diuretics at levels which do not alter the animals’ blood pressure does not alter the timing or incidence of stroke development, and does not prolong the lifespan of the animals after stroke has developed.

1. The plasma concentration of hyaluronate (hyaluronic acid; HA) was measured in different vascular beds in order to determine regional kinetics of endogenous HA in fasting, supine subjects with normal ( n = 6) or moderately decreased kidney function ( n = 9). 2. In both groups hepatic venous HA was significantly below the value obtained in plasma from pulmonary artery, inferior vena cava, and renal veins ( P < 0.001), giving a net hepato-splanchnic extraction ratio of HA about 33%. 3. The concentration of HA in renal veins was significantly below that of the pulmonary artery and inferior vena cava ( P < 0.05). Average net renal extraction ratio of HA in normal kidneys was approximately 20%. Unilateral kidney function was assessed by 131 I-hippuran renography, and the kidney with better function had a significantly higher extraction ratio when compared with the kidney with the lower function ( P < 0.025). HA was inversely correlated to glomerular filtration rate ( r = − 0.59, P < 0.02). 4. Assuming a plasma flow of 800 and 600 ml/min in normal liver and kidneys, respectively, the average normal plasma clearances of HA in these organs in the resting subject may be estimated to be 250 and 120 ml/min, respectively. 5. The results indicate that the hepato-splanchnic region normally plays a major role in the bio-degradation of endogenous circulating HA. The kidneys also eliminate the compound, presumably the low-molecular-weight fraction of the material. The results may explain abnormally high values of circulating HA in patients with diseases in these organs.

1. An oral water load of 20 ml/kg body wt. was given to eight patients with nephrotic syndrome before and after remission of the syndrome, and to 13 healthy control subjects. Urine volume ( D ), free water clearance ( C water ), plasma concentrations of arginine vasopressin (AVP), angiotensin II (ANG II) and aldosterone (Aldo), were determined before and three times during the first 4 h after loading. 2. D and C water increased to a significantly lower level ( P < 0.01) after water loading in patients with nephrotic syndrome than in control subjects, but D and C water were normal after remission of the syndrome. The maximum increase in C water (ΔC water max. ) was 1.07 ml/min (median) before remission and 7.93 ml/min after, compared with 8.01 ml/min in the control group. 3. Creatinine clearance ( C cr ) increased significantly after remission (63 ml/min to 88 ml/min, P < 0.01), and the fractional excretion of sodium was enhanced. AVP was higher in the nephrotic syndrome both before (2.9 pmol/l) and after remission (2.9 pmol/l) compared with the control group (1.8 pmol/l). ANG II and Aldo did not change after remission and remained at the same level as in the control group. 4. The elevation in ΔC water max after remission was accompanied by an increase in C cr in all patients and ΔC water max. and C cr were significantly correlated (ρ = 0.600, n = 16, P < 0.05). No relationship was found between the change in Δ C water max. and ANG II and Aldo. 5. AVP was significantly suppressed in patients with nephrotic syndrome before remission, but not after remission nor in control subjects, so that although AVP did not differ in nephrotic patients before and after remission, AVP cannot be excluded as a contributory factor to the reduction in C water in the nephrotic syndrome. 6. It is concluded that patients with nephrotic syndrome excrete an oral water load slower than control subjects and that the excretion rate is normal after remission of the syndrome. It is suggested that the normalization of C water may be attributed to an increase in glomerular filtration rate or a decrease in proximal tubular sodium reabsorption, although a possible role for AVP has not been excluded.

1. Plasma from hypervolaemic rats was fractionated on a G-200 Sephadex column. In addition to three different protein peaks, a fourth non-protein fraction was obtained. Each of the four peaks was desalted, freeze-dried, reconstituted and injected into normal anaesthetized rats. Significant natriuretic responses resulted, from injection, of the middle protein peak and of the small-molecular-weight peak. It was concluded that a natriuretic humoral factor was present in the blood of hypervolaemic rats, and that this factor was of low molecular weight but normally occurred bound to plasma protein. 2. The renal response to injection of non-protein fraction, obtained from either hypervolaemic donors or from iso- or hypo-volaemic donors, was compared in two groups of bioassay rats to test whether the natriuretic factor was present only in plasma of the blood-volume-expanded animals. Both types of reconstituted fraction caused diuresis, natriuresis and kaliuresis in bioassay animals. Only the natriuretic response was statistically greater when the fraction obtained from hypervolaemic plasma was used. In addition to non-specific increase in fluid and ion excretion, possibly due to the extraction and/or methodological procedures, these results demonstrate that blood-volume expansion releases a humoral natriuretic factor into plasma. Since there were no increases in filtration rate, the factor specifically inhibited tubular sodium re-absorption. 3. To determine the maximum possible effect of the non-protein factor, the dose given to bioassay rats was tripled. There was no further increase in sodium excretion, indicating that the effect was quantitatively limited and suggesting that the physiological importance of natriuretic hormone lies in long-term regulation of body-fluid balance.

1. The effects of unilateral nephrectomy on urinary concentration and dilution were studied in Sprague—Dawley rats. To exclude incomplete suppression of antidiuretic hormone, free water formation was also studied in rats with congenital diabetes insipidus (Brattleboro strain). 2. Urinary solute-free water formation was similar in Sprague—Dawley and Brattleboro rats. Unineph-rectomized animals excreted a water load promptly and diluted their urine to the same degree as control rats. Maximal values for C water and T Cwater per kidney were higher after nephrectomy, but were similar to those of control rats at comparable rates of fluid delivery to the distal nephron. Renal tissue osmolality was similar in uninephrectomized and sham-operated animals, indicating that non-antidiuretic hormone-dependent backflux of filtrate was the same in the two groups. The only defect observed in uninephrectomized animals was a small reduction in maximal urine osmolality. 3. These results demonstrate that free water formation and reabsorption are unaffected by unilateral nephrectomy and suggest that, in the remaining kidney, filtrate reabsorption along the entire nephron increases in proportion to the increment in glomerular filtration.