Hypertensive nephrosclerosis: wider kidney biopsy indications may be needed to improve diagnostics

Background Hypertensive nephrosclerosis is the presumed underlying cause in many end‐stage kidney disease (ESKD) patients, but the diagnosis is disputed and based on clinical criteria with low diagnostic accuracy. Objective To evaluate and improve the diagnostic process for nephrosclerosis patients. Methods We included adults from the population‐based HUNT study (n = 50 552), Norwegian CKD patients referred for kidney biopsy 1988–2012 (n = 7261), and unselected nephrology clinic patients (n = 193) used for matching. Decision tree analysis and ROC curve‐based methods of optimal cut‐offs were used to improve clinical nephrosclerosis criteria. Results Nephrosclerosis prevalence was 2.7% in the general population, and eGFR decline and risk for kidney‐related hospital admissions and ESKD were comparable to patients with diabetic kidney disease. In the biopsy cohort, current clinical criteria had very low sensitivity (0.13) but high specificity (0.94) for biopsy‐verified arterionephrosclerosis. A new optimized diagnostic algorithm based on proteinuria (155 mm Hg) and age (>75 years) only marginally improved diagnostic accuracy (sensitivity 0.19, specificity 0.96). Likewise, there were still false‐positive cases with treatable diagnoses like glomerulonephritis, interstitial nephritis and others (40% of all test positive). Decision curve analysis showed that the new criteria can lead to higher clinical utility, especially for patients considering the potential harms to be close to the potential benefits, while the more risk‐tolerant ones (harm:benefit ratio < 1:4) should consider kidney biopsy. Conclusion Further improvements of the current clinical criteria seem difficult, so risks and benefits of kidney biopsy could be more actively discussed with selected patients to reduce misclassification and direct treatment.publishedVersio

Hypertensive nephrosclerosis: wider kidney biopsy indications may be needed to improve diagnostics

Background Hypertensive nephrosclerosis is the presumed underlying cause in many end‐stage kidney disease (ESKD) patients, but the diagnosis is disputed and based on clinical criteria with low diagnostic accuracy. Objective To evaluate and improve the diagnostic process for nephrosclerosis patients. Methods We included adults from the population‐based HUNT study (n = 50 552), Norwegian CKD patients referred for kidney biopsy 1988–2012 (n = 7261), and unselected nephrology clinic patients (n = 193) used for matching. Decision tree analysis and ROC curve‐based methods of optimal cut‐offs were used to improve clinical nephrosclerosis criteria. Results Nephrosclerosis prevalence was 2.7% in the general population, and eGFR decline and risk for kidney‐related hospital admissions and ESKD were comparable to patients with diabetic kidney disease. In the biopsy cohort, current clinical criteria had very low sensitivity (0.13) but high specificity (0.94) for biopsy‐verified arterionephrosclerosis. A new optimized diagnostic algorithm based on proteinuria (155 mm Hg) and age (>75 years) only marginally improved diagnostic accuracy (sensitivity 0.19, specificity 0.96). Likewise, there were still false‐positive cases with treatable diagnoses like glomerulonephritis, interstitial nephritis and others (40% of all test positive). Decision curve analysis showed that the new criteria can lead to higher clinical utility, especially for patients considering the potential harms to be close to the potential benefits, while the more risk‐tolerant ones (harm:benefit ratio < 1:4) should consider kidney biopsy. Conclusion Further improvements of the current clinical criteria seem difficult, so risks and benefits of kidney biopsy could be more actively discussed with selected patients to reduce misclassification and direct treatment

Hypertensive nephrosclerosis: wider kidney biopsy indications may be needed to improve diagnostics

Background. Hypertensive nephrosclerosis is the presumed underlying cause in many end-stage kidney disease (ESKD) patients, but the diagnosis is disputed and based on clinical criteria with low diagnostic accuracy. Objective. To evaluate and improve the diagnostic process for nephrosclerosis patients. Methods. We included adults from the populationbased HUNT study (n = 50 552), Norwegian CKD patients referred for kidney biopsy 1988–2012 (n = 7261), and unselected nephrology clinic patients (n = 193) used for matching. Decision tree analysis and ROC curve-based methods of optimal cut-offs were used to improve clinical nephrosclerosis criteria. Results. Nephrosclerosis prevalence was 2.7% in the general population, and eGFR decline and risk for kidney-related hospital admissions and ESKD were comparable to patients with diabetic kidney disease. In the biopsy cohort, current clinical criteria had very low sensitivity (0.13) but high specificity (0.94) for biopsy-verified arterionephrosclerosis. A new optimized diagnostic algorithm based on proteinuria (<0.75 g d 1 ), systolic blood pressure (>155 mm Hg) and age (>75 years) only marginally improved diagnostic accuracy (sensitivity 0.19, specificity 0.96). Likewise, there were still false-positive cases with treatable diagnoses like glomerulonephritis, interstitial nephritis and others (40% of all test positive). Decision curve analysis showed that the new criteria can lead to higher clinical utility, especially for patients considering the potential harms to be close to the potential benefits, while the more risk-tolerant ones (harm:benefit ratio < 1:4) should consider kidney biopsy. Conclusion. Further improvements of the current clinical criteria seem difficult, so risks and benefits of kidney biopsy could be more actively discussed with selected patients to reduce misclassification and direct treatment

Clinical phenotypes and long-term prognosis in white patients with biopsy-verified hypertensive nephrosclerosis

Introduction Hypertensive nephrosclerosis is considered the second most common cause of end-stage renal disease (ESRD), but it is still an insufficiently studied and controversial disease entity. More information on the phenotype and prognosis is needed to improve clinical diagnostics and treatment. Methods We included all Norwegian patients with chronic kidney disease (CKD) referred for kidney biopsy between 1988 and 2012 whose clinical presentation was consistent with, but not primarily suspicious for, hypertensive nephrosclerosis (n = 4920); follow-up continued until 2013. Results A total of 918 patients (19%) had biopsy-verified hypertensive nephrosclerosis (i.e., arterionephrosclerosis). Their most common biopsy indications were proteinuria (57%), low estimated glomerular filtration rate (eGFR) (44%), hematuria (34%), or combinations of these indications. Multivariable logistic regression analysis revealed that arterionephrosclerosis was significantly associated with higher age, male sex, not having diabetes, higher blood pressure, lower proteinuria, and not having hematuria (P 0.05 for all). The most common biopsy-verified diagnoses in patients fulfilling the clinical criteria for hypertensive nephrosclerosis were arterionephrosclerosis (40%), glomerulonephritis (22%), and interstitial nephritis (14%), reflecting that the criteria had low sensitivity (0.17) and high specificity (0.94). ESRD and mortality risks did not differ in patients with arterionephrosclerosis compared to patients with glomerulonephritis, interstitial nephritis, or other relevant diagnoses (P > 0.1 for both), whereas patients with diabetic kidney disease had a 2-fold higher risk (P < 0.001 for both). Conclusion Arterionephrosclerosis is a high-risk disease, often with an atypical phenotype with proteinuria and hematuria contributing to low accuracy for current clinical criteria for hypertensive nephrosclerosis

Clinical phenotypes and long-term prognosis in white patients with biopsy-verified hypertensive nephrosclerosis

Introduction Hypertensive nephrosclerosis is considered the second most common cause of end-stage renal disease (ESRD), but it is still an insufficiently studied and controversial disease entity. More information on the phenotype and prognosis is needed to improve clinical diagnostics and treatment. Methods We included all Norwegian patients with chronic kidney disease (CKD) referred for kidney biopsy between 1988 and 2012 whose clinical presentation was consistent with, but not primarily suspicious for, hypertensive nephrosclerosis (n = 4920); follow-up continued until 2013. Results A total of 918 patients (19%) had biopsy-verified hypertensive nephrosclerosis (i.e., arterionephrosclerosis). Their most common biopsy indications were proteinuria (57%), low estimated glomerular filtration rate (eGFR) (44%), hematuria (34%), or combinations of these indications. Multivariable logistic regression analysis revealed that arterionephrosclerosis was significantly associated with higher age, male sex, not having diabetes, higher blood pressure, lower proteinuria, and not having hematuria (P 0.05 for all). The most common biopsy-verified diagnoses in patients fulfilling the clinical criteria for hypertensive nephrosclerosis were arterionephrosclerosis (40%), glomerulonephritis (22%), and interstitial nephritis (14%), reflecting that the criteria had low sensitivity (0.17) and high specificity (0.94). ESRD and mortality risks did not differ in patients with arterionephrosclerosis compared to patients with glomerulonephritis, interstitial nephritis, or other relevant diagnoses (P > 0.1 for both), whereas patients with diabetic kidney disease had a 2-fold higher risk (P < 0.001 for both). Conclusion Arterionephrosclerosis is a high-risk disease, often with an atypical phenotype with proteinuria and hematuria contributing to low accuracy for current clinical criteria for hypertensive nephrosclerosis