Nahid Tabibzadeh1, Sandra Wagner2, Marie Metzger3, Martin Flamant4, Pascal Houillier5, Jean-Jacques Boffa6, Francois Vrtovsnik7, Eric Thervet8, Bénédicte Stengel9, Jean-Philippe Haymann1. 1. Sorbonne Université, Inserm UMR_S 1155, Paris, France; Unit of Renal Physiology, AP-HP Hôpital Tenon, Paris, France. 2. CESP, Inserm U1018, Univ Paris-Saclay, Univ Paris-Sud, UVSQ, Villejuif, France; FCRIN INI-CRCT, France. 3. CESP, Inserm U1018, Univ Paris-Saclay, Univ Paris-Sud, UVSQ, Villejuif, France. 4. Université Paris Diderot, Paris, France; Unit of Renal Physiology, AP-HP Hôpital Bichat, Paris, France. 5. Université Paris Descartes, INSERM UMR_S1138, Paris, France; Unit of Renal Physiology, AP-HP Hôpital Européen Georges Pompidou, Paris, France. 6. Sorbonne Université, Inserm UMR_S 1155, Paris, France; Unit of Nephrology, AP-HP Hôpital Tenon, Paris, France. 7. Université Paris Diderot, Paris, France; Unit of Nephrology, AP-HP Hôpital Bichat, Paris, France. 8. Université Paris Descartes, INSERM UMR_S1138, Paris, France; Unit of Nephrology, AP-HP Hôpital Européen Georges Pompidou, Paris, France. 9. CESP, Inserm U1018, Univ Paris-Saclay, Univ Paris-Sud, UVSQ, Villejuif, France; FCRIN INI-CRCT, France. Electronic address: benedicte.stengel@inserm.fr.
Abstract
RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD). STUDY DESIGN: Prospective longitudinal cohort study. SETTING & PARTICIPANTS: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study. PREDICTOR: Fasting urinary osmolality measured using delta cryoscopy. OUTCOMES: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance. ANALYTICAL APPROACH: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR. RESULTS: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile. LIMITATIONS: Fasting was self-reported. CONCLUSIONS: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.
RATIONALE & OBJECTIVE:Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD). STUDY DESIGN: Prospective longitudinal cohort study. SETTING & PARTICIPANTS: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study. PREDICTOR: Fasting urinary osmolality measured using delta cryoscopy. OUTCOMES: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance. ANALYTICAL APPROACH: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR. RESULTS: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile. LIMITATIONS: Fasting was self-reported. CONCLUSIONS: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.
Authors: Bernhard Kreft; Judith Bergs; Mehrgan Shahryari; Leon Alexander Danyel; Stefan Hetzer; Jürgen Braun; Ingolf Sack; Heiko Tzschätzsch Journal: Front Physiol Date: 2021-01-11 Impact factor: 4.566