Background

Higher muscle mass is associated with better outcomes and longevity in patients with chronic disease states. Imaging studies such as dual-energy X-ray absorptiometry (DEXA) are among the gold standard methods for assessing body fat and lean body mass (LBM), approximately half of which is comprised of skeletal muscle mass. Elaborate imaging devices, however, are not commonly available in routine clinical practice and therefore easily accessible and cost-effective, but reliable muscle mass biomarkers are needed. One such marker is serum creatinine, derived from muscle-based creatine, which is inexpensive and ubiquitously available, and it can serve as a biomarker of skeletal muscle mass in human subjects.

Methods and results

In 118 hemodialysis patients, we found that the 3-month averaged serum creatinine concentration correlated well with DEXA-measured LBM. The recent literature regarding serum creatinine as a surrogate of muscle mass is summarized, as is the literature concerning the use of other measures of muscle mass, such as plasma gelsolin and actin, and urinary creatinine excretion. We have also reviewed the role of dietary meat intake in serum creatinine variability along with several biomarkers of dietary meat intake (creatine, carnitine, carnosine, ophidine, anserine, 3-methyl-L-histidine and 1-methylhistidine).

Conclusion

In summary, none of these biomarkers was studied in CKD patients. We advance the hypothesis that in both health and disease, under steady state, serum creatinine can serve as a reliable muscle mass biomarker if appropriate adjustment for full or residual kidney function and dietary meat intake is undertaken.

Background

In hemodialysis patients, higher serum creatinine (Cr) concentration represents larger muscle mass and predicts greater survival. However, this association remains uncertain in peritoneal dialysis (PD) patients.

Methods

In a cohort of 10 896 PD patients enrolled from 1 July 2001 to 30 June 2006, the association of baseline serum Cr level and change during the first 3 months after enrollment with all-cause mortality was examined.

Results

The cohort mean ± SD age was 55 ± 15 years old and included 52% women, 24% African-Americans and 48% diabetics. Compared with patients with serum Cr levels of 8.0–9.9 mg/dL, patients with serum Cr levels of <4.0 mg/dL and 4.0–5.9 mg/dL had higher risks of death {HR 1.36 [95% confidence interval (95% CI) 1.19–1.55] and 1.19 (1.08–1.31), respectively} whereas patients with serum Cr levels of 10.0–11.9 mg/dL, 12.0–13.9 mg/dL and ≥14.0 mg/dL had lower risks of death (HR 0.88 [95% CI 0.79–0.97], 0.71 [0.62–0.81] and 0.64 [0.55–0.75], respectively) in the fully adjusted model. Decrease in serum Cr level over 1.0 mg/dL during the 3 months predicted an increased risk of death additionally. The serum Cr–mortality association was robust in patients with PD treatment duration of ≥12 months, but was not observed in those with PD duration of <3 months.

Conclusions

Muscle mass reflected in serum Cr level may be associated with survival even in PD patients. However, the serum Cr–mortality association is attenuated in the early period of PD treatment, suggesting competing effect of muscle mass versus residual renal function on mortality.

Vascular endothelial growth factor (VEGF) inhibition can cause worsening hypertension, proteinuria, chronic kidney injury, and glomerular disease. Thrombotic microangiopathy (TMA) and other nephrotic disorders have been reported with systemic VEGF blockade. These same agents are given intravitreally for age-related macular degeneration (AMD) and diabetic retinopathy (DR), albeit at lower doses than those given for systemic indications. Systemic absorption of anti-VEGF agents when given intravitreally has been shown consistently along with evidence of significant intravascular VEGF suppression. While worsening hypertension has only been seen in some large-scale studies, case reports show worsening proteinuria and diverse glomerular diseases. These include TMA-associated lesions like focal and segmental glomerulosclerosis with collapsing features (cFSGS). In this paper, we report three cases of TMA likely associated with the use of intravitreal anti-VEGF therapy. These patients developed the signature lesion of VEGF blockade in a 6 to 11 month time frame after starting intravitreal VEGF inhibitors. The literature is reviewed showing similar cases. Intravitreal VEGF blockade may cause these adverse events in a hitherto unidentified subgroup of patients. Well-controlled prospective observational trials are needed to determine the event rate and identify which subgroups of patients are at increased risk. A registry for patients who develop worsening hypertension, proteinuria exacerbation, and glomerular diseases from intravitreal VEGF blockade is proposed.