Nephrin as a biomarker of sickle cell glomerulopathy in Malawi

Heimlich, J. Brett; Chipoka, Godwin; Elsherif, Laila; David, Emeraghi; Ellis, Graham; Kamthunzi, Portia; Krysiak, Robert; Mafunga, Pilirani; Zhou, Qingning; Cai, Jianwen; Gopal, Satish; Key, Nigel S.; Ataga, Kenneth I.

doi:10.1002/pbc.26993

Cited by 14 publications

(17 citation statements)

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“…Table 3. Biomarkers investigated for use in sickle cell nephropathy Proposed potential markers for early detection and monitoring progression of SCN Urine microalbumin/creatinine ratio Urine total protein/creatinine ratio Urine N-acetyl-beta-D-glucosaminidase (NAG) [24,89] Urine kidney injury molecule-1 [24,89] Urine ceruloplasmin [90] Urine free hemoglobin [29] Urine nephrin [91] Plasma soluble FMS-like tyrosine kinase-1 (sFLT-1) [92] Plasma cystatin C [89,93] Measured glomerular filtration rate using iohexol clearance [94] Markers with conflicting or negative data on association with proteinuria in SCN Urine neutrophil gelatinase-associated lipocalin (NGAL) [63,89,95] Urine transforming growth factor beta (TGFβ) [63,89,95] Urine liver-type fatty acid binding protein (L-FABP) [89] Urine endothelin-1 [24] Olaniran/Eneanya/Nigwekar/VelaParada/Achebe/Sharma/Thadhani Non-Pharmacologic Therapies The evidence for the non-pharmacological therapies in SCN is sparse. In particular, chronic blood transfusions early in childhood have been shown to be reno-protective in children [15], but it is not clear how long this effect lasts.…”

Section: Current Therapies For Scn (Table 4)mentioning

confidence: 99%

Sickle Cell Nephropathy in the Pediatric Population

et al. 2018

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Background: Compared to the past, patients with sickle cell disease (SCD) currently live longer due to improvements in diagnosis and comprehensive care. Due to these advances, long-term chronic complications pose a greater challenge in the management of patients with SCD. In particular, sickle cell nephropathy (SCN) is associated with significant morbidity and mortality across all age groups. Furthermore, SCN is an understudied condition with relatively few symptoms and therefore requires close surveillance. In this review, we sought to explore the epidemiology, natural history, and treatment options for SCN with an emphasis on the pediatric population. Summary: SCN invariably begins in childhood with evidence of structural changes detected as early as infancy. These indolent changes can progress undetected to advanced chronic kidney disease by late adolescence or early adulthood. The risk factors for progression are not well defined, but significant albuminuria (which is also the most common presentation in childhood) is a key factor in progression. One of the main challenges in understanding SCN in children is the poor correlation between estimated and measured glomerular filtration rates. Another challenge is the lack of large-scale longitudinal studies that track the clinical outcomes of pediatric patients over time. Several studies aim to identify early biomarkers of SCN in children, as albuminuria presents only following significant chronic damage. The utility of angiotensin converting enzyme inhibitors and hydroxyurea in treating albuminuria is addressed here as well as novel treatments that may be of benefit.

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Section: Current Therapies For Scn (Table 4)mentioning

confidence: 99%

Sickle Cell Nephropathy in the Pediatric Population

et al. 2018

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“…1 Albuminuria, which represents an early stage of chronic kidney disease (CKD), starts in childhood and may predict early mortality in SCA. [4][5][6][7][8][9] CKD occurs in ;30% of adult SCA patients and is associated with a higher risk of mortality when resulting from SCA compared with other causes of CKD. 10,11 Once end-stage renal disease (ESRD) is recognized, the 1-year mortality rate is 3 times higher among patients with SCA compared with non-SCA individuals.…”

Section: Introductionmentioning

confidence: 99%

Progression of albuminuria in patients with sickle cell anemia: a multicenter, longitudinal study

et al. 2020

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Sickle cell nephropathy results in chronic kidney disease (CKD), which is associated with significant morbidity and mortality in sickle cell anemia (SCA). Albuminuria is an early manifestation of sickle nephropathy; however, little is known about progression of albuminuria or its correlation with glomerular filtration rate (GFR) decline or CKD. We studied nephropathy progression in 303 SCA participants in a prospective, multicenter, longitudinal study. We collected steady-state urine and serum samples yearly and assessed albumin/creatinine ratio (ACR), estimated GFR (eGFR), and SCA and nephropathy biomarkers. Participants with albuminuria (ACR ≥30 mg/g) for ≥2 annual measurements were classified as having persistent albuminuria (PA). At baseline (mean age, 21 years; range, 2-64 years), 32% had albuminuria. In longitudinal multivariate analysis, ACR was associated with sex, anemia, older age, and higher bilirubin and kidney injury molecule-1 levels. Albuminuria increased with age by 3.5 mg/g per year (P < .0001). Of 175 participants with ≥3 annual samples, 81% with baseline albuminuria ≥100 mg/g developed PA. Decreased eGFR and adult CKD were associated with PA (P = .002 and P = .02, respectively), but not with baseline albuminuria. Rate of eGFR decline was steeper among adults (but not children) with albuminuria, compared with those without (P = .02). Participants with PA were more likely to have rapid eGFR decline compared with those without (P = .03). In this longitudinal study, albuminuria progressed with age, and adults with albuminuria had worse eGFR decline than those without. Albuminuria ≥100 mg/g predicted PA, which was associated with rapid eGFR decline and CKD development in adults with SCA. This trial was registered at www.clinicaltrials.gov as #NCT02239016.

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“…Moreover, additional crosssectional studies have demonstrated the presence of elevated renal injury biomarkers in young SCD patients. 7,[13][14][15] Elevations in tubular injury markers are associated with glomerular injury, 16 highlighting potential tubular alterations happening prior to glomerulopathy, and suggesting a tubuloglomerular mechanism of kidney injury in SCD. However, critically absent is evidence to demonstrate the characteristics of primary pathophysiological processes involved in kidney injury and the natural course of the renal disease in SCD.…”

Section: Introductionmentioning

confidence: 99%