Modification of the impact of hypertension on proteinuria by renal arteriolar hyalinosis in nonnephrotic chronic kidney disease

Zamami, Ryo; Kohagura, Kentaro; Miyagi, Tsuyoshi; Kinjyo, Takanori; Shiota, Kazutaka; Ohya, Yusuke

doi:10.1097/hjh.0000000000001091

Cited by 17 publications

(11 citation statements)

References 15 publications

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“…In a previous study on patients with IgA nephropathy, including many young patients aged <30 years, we reported that blood pressure-dependent reduction in eGFR was higher among those with renal arteriolar hyalinosis than in those without hyalinosis. 9 Therefore, our findings suggest that renal arterio-arteriolosclerosis should be considered a potential risk factor for renal dysfunction even in younger patients with CKD who may not have hypertension and diabetes mellitus.…”

mentioning

confidence: 66%

“…The current study's findings have significant clinical relevance considering that hyalinosis may be a marker of disrupted autoregulation of glomerular hemodynamics 8 and may potentiate susceptibility to blood pressure-dependent glomerular damage, 9 which is considered a mechanism of CKD progression. In a previous study on patients with IgA nephropathy, including many young patients aged <30 years, we reported that blood pressure-dependent reduction in eGFR was higher among those with renal arteriolar hyalinosis than in those without hyalinosis.…”

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confidence: 84%

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Age-related Changes in Renal Arterio-Arteriolosclerosis in Kidney Disease: Renal Biopsy-based Study

Oshiro

Kohagura

Kanamitsu

et al. 2022

Kidney International Reports

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confidence: 66%

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confidence: 84%

Age-related Changes in Renal Arterio-Arteriolosclerosis in Kidney Disease: Renal Biopsy-based Study

Oshiro

Kohagura

Kanamitsu

et al. 2022

Kidney International Reports

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“…This may be caused in part by a tendency toward more afferent arteriolar hyalinosis with advancing CKD. 29 Mesangial cell contraction caused by RAAS activation leading to a decreased capillary surface area also could contribute to decreased SNGFR without reducing mean GV. 30 Of note, SNUPE was much higher in the ORG subgroups with more advanced CKD stages.…”

Section: Discussionmentioning

confidence: 99%

Single-Nephron GFR in Patients With Obesity-Related Glomerulopathy

Okabayashi

Tsuboi

Sasaki

et al. 2020

Kidney International Reports

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Introduction: Obesity-related glomerulopathy (ORG) is a slowly progressive kidney disease occurring in association with obesity. It is characterized histopathologically by glomerulomegaly, likely caused by single-nephron hyperfiltration that has not been demonstrated in humans because of technical difficulty in measuring single-nephron glomerular filtration rate (SNGFR) in the clinical setting. Methods: Total glomerular number per kidney, with or without global glomerulosclerosis, was estimated by the combination of cortical volume assessment via unenhanced computed tomography and biopsybased stereology. Mean glomerular volume was calculated from the measured area of glomerular tufts. Both SNGFR and single-nephron urinary protein excretion (SNUPE) were estimated by dividing values for estimated glomerular filtration rate and urinary protein excretion by the number of nonsclerotic glomeruli. Living kidney donors were used as healthy controls. Results: A total of 48 ORG patients with average nonsclerotic glomerular numbers of 456,000 AE 235,000 per kidney were included. The values for SNGFR in ORG patients with chronic kidney disease (CKD) stages 1 and 2 were higher than for nonobese and obese controls (97 AE 43 vs. 59 AE 21 vs. 64 AE 21 nl/min, respectively, P ¼ 0.001). Nonsclerotic glomerular number decreased with advancing stages of renal functional impairment. The presence of ORG with more advanced CKD stages was associated with lower SNGFR and marked elevation in SNUPE levels, with no difference in the mean glomerular volume between the stages. Conclusions: These results provide functional evidence for single-nephron hyperfiltration in patients with ORG, and identify compensatory failure to maintain effective SNGFR as a feature of advanced-stage ORG.

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“…Therefore, even a normal range of systemic blood pressure might be associated with glomerular hypertension and might result in increased proteinuria. We recently reported that hyalinosis in renal arterioles, a potential marker for dysregulation of the autoregulation system, was associated with higher urinary protein levels and greater reductions in eGFR than those seen in patients without hyalinosis, even within the normal range of blood pressure in IgA nephropathy [ 39 ]. Moreover, we reported that uric acid may augment susceptibility for hypertensive glomerular damage in association with evoking renal arteriolopathy in IgA nephropathy [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Add-On Effect of Angiotensin Receptor Blockade (Candesartan) on Clinical Remission in Active IgA Nephropathy Patients Treated with Steroid Pulse Therapy and Tonsillectomy: a Randomized, Parallel-Group Comparison Trial

Kohagura

Arima

Miyasato

et al. 2018

Kidney Blood Press Res

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Background/Aims: Angiotensin receptor blockers (ARBs) may be beneficial for clinical remission during conventional therapy with tonsillectomy and steroid pulse (TSP) for active IgA nephropathy. Methods: Seventy-seven patients with active IgA nephropathy were randomly assigned to the control arm with conventional regimen (TSP followed by oral prednisolone) (n = 37) or the ARB arm with conventional regimen plus ARB candesartan for the first 6 months (n = 40). Patients not achieving proteinuria remission at 12 months in either arm were administered candesartan, which was titrated until the 24-month follow-up. The primary endpoints were remission of proteinuria (< 0.3 g/gCr) and hematuria at 12 months. Results: Baseline proteinuria (g/g Cr) were comparable between the control and ARB arm (1.02 vs. 0.97, P = 0.97). Similarly, cumulative remission rates at 6, 12, and 24 months were comparable between the control and ARB arms (37.8% vs. 35% [P = 0.80], 48.7% vs. 38.5% [P = 0.37], 71.4% vs. 51.3% [P = 0.08]). Proteinuria, which was slightly worse in the control arm than in the ARB arm at 6 months, was comparable afterwards (0.20 vs. 0.23 g/g Cr at 12 months; 0.12 vs. 0.13 g/g Cr at 24 months). Significant reductions observed in urinary angiotensinogen were almost comparable between the two treatment arms at both 6 and 12 months. Conclusion: Early candesartan treatment combined with TSP may not benefit clinical remission regardless of the blood pressure. ARB titration later during the treatment might provide benefit for patients with active IgA nephropathy.

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Modification of the impact of hypertension on proteinuria by renal arteriolar hyalinosis in nonnephrotic chronic kidney disease

Abstract: Renal arteriolar hyalinosis may potentiate susceptibility to BP-related glomerular damage in patients with nonnephrotic CKD. Dysregulated afferent arteriolar resistance via arteriolar sclerosis may affect hypertensive renal damage.

Cited by 17 publications

References 15 publications

Age-related Changes in Renal Arterio-Arteriolosclerosis in Kidney Disease: Renal Biopsy-based Study

Age-related Changes in Renal Arterio-Arteriolosclerosis in Kidney Disease: Renal Biopsy-based Study

Single-Nephron GFR in Patients With Obesity-Related Glomerulopathy

Add-On Effect of Angiotensin Receptor Blockade (Candesartan) on Clinical Remission in Active IgA Nephropathy Patients Treated with Steroid Pulse Therapy and Tonsillectomy: a Randomized, Parallel-Group Comparison Trial

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