Renal function in children and adolescents with Duchenne muscular dystrophy

Abstract

Improved life expectancy and the need for robust tools to monitor renal safety of emerging new therapies have fueled the interest in renal function in Duchenne muscular dystrophy (DMD) patients. We aimed to establish a methodology to accurately assess their renal function. Twenty DMD patients (5-22 years) were included in this prospective study. After obtaining medical history, all patients underwent a clinical examination, 24-hour ambulatory blood pressure monitoring, ultrasound of the kidneys, direct GFR measurement ( 51 Cr-EDTA, mGFR), complete blood and urine analysis. Seventeen of 20 patients were treated with corticosteroids and 5/20 with angiotensin converting enzyme inhibitor (lisinopril). No patient suffered from urinary tract infections or other renal diseases. Hypertension (systolic or diastolic blood pressure >P95) was found in 9/20 patients (8/9 patients were on steroid treatment) and a non-dipping blood pressure profile in 13/20 subjects (10/13 patients were on steroid treatment). Urinary protein to creatinine ratio was elevated in 17/18 patients, whereas 24-hour urine protein excretion was normal in all subjects. Median interquartile range (IQR) mGFR was 130.4 (29.1) mL/min/1.73 m 2 . Hyperfiltration (mGFR >150 mL/min/1.73 m 2 ) was found in 5/20 patients. Inverse correlation between mGFR and age was observed (R 2 = 0.45, p = 0.001). Serum creatinine based estimated GFR (eGFR) equations overestimated mGFR up to 300%. eGFR based on cystatin C Filler equation was closest to the mGFR (median eGFR (IQR) of 129.5 (39.7) mL/min/1.73 m 2 ). Our study demonstrates a high prevalence of hyperfiltration and hypertension in children and adolescents with DMD. Because the majority of hypertensive patients were under corticosteroid treatment, the iatrogenic cause of hypertension cannot be excluded. Serum or urine creatinine measurements are of no value to evaluate renal function in DMD patients due to the reduced skeletal muscle mass.

Treatable renal failure found in non-ambulatory Duchenne muscular dystrophy patients

“…Serum BUN and CysC levels lay outside the reference range at the renal dysfunction time, but the change in Cr was so subtle that even the higher value did not exceed the normal range. These findings are in agreement with a proposal that CysC and its related equations are more reliable renal markers in DMD patients [7,9]. Although the effect of corticosteroids on CysC levels remain unclear [10,11], none of the four patients here were taking corticosteroids at the time of renal failure.…”

“…eGFRCys measurement is based on serum CysC level [8], and in DMD patients, eGFRCys correlates better with GFR, as measured by 51 Cr-EDTA than the serum Cr-based equation [9]. The four cases reported here all had higher serum BUN, CysC, and Cr levels compared with previous studies.…”

The Clinical Outcome Study for dysferlinopathy

“…9,32–35 Low serum creatinine seen in 70% of patients is relevant for renal function monitoring, as creatinine-dependent methods will be uninformative. 36 …”

Measurement and Estimation of Glomerular Filtration Rate in Children

“…In high-risk populations with reduced muscle mass such as oncology patients, hematopoietic stem cell transplant recipients, spina bifida/muscular dystrophy, and spinal cord injury patients, cystatin C–based formulas seem to more accurately estimate the measured GFR than creatinine-based equations. 45-49 The univariate cystatin C equation for children with CKD to facilitate use in the clinical setting 33 is as follows: $$\text{eGFR}=70.69\times false[{false(\text{cystatin}\mathrm{normalC})}^{-0.931}false]$$…”