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Middle molecule and small protein removal in children on peritoneal dialysis
Giovanni Montini1, Gianpaolo Amici, Sabrina Milan
1Nephrology, Dialysis and Transplant Unit, Pediatric Department, University-Hospital, Via Giustiniani 3, 35128 Padua, Italy. montini@pediatria.unipd.it
Insights
Peritoneal dialysis (PD) in children effectively removes solutes up to 15 kD, with residual renal function significantly contributing to the clearance of larger molecules like inulin and beta2-microglobulin (beta2m). Anuric patients require closer monitoring for middle molecule accumulation.
Area of Science:
- Nephrology
- Pediatric Nephrology
- Dialysis Technology
Background:
- Dialysis efficiency is crucial for patient outcomes, particularly in children undergoing peritoneal dialysis (PD).
- Limited data exist on the removal of solutes with molecular weights exceeding urea and creatinine during PD.
- Understanding solute transport is key to optimizing PD therapy in pediatric patients.
Purpose of the Study:
- To assess the transport and removal of substances up to 15 kD in pediatric PD patients.
- To evaluate the specific contribution of residual renal function to solute clearance in these patients.
- To compare solute removal in anuric versus non-anuric children on PD.
Main Methods:
- Seventeen pediatric patients on automated PD were studied, divided into non-anuric (with residual diuresis) and anuric groups.
- A single-injection inulin clearance test was performed during a standardized nightly intermittent PD (NIPD) session.
- Measurements included urea, creatinine, inulin, cystatin C, and beta2-microglobulin (beta2m) in blood, urine, and dialysate, with subsequent calculation of clearances and solute removal indices (SRI).
Main Results:
- Clearances for all studied solutes (urea, creatinine, inulin, beta2m, cystatin C) were generally higher in non-anuric patients compared to anuric patients.
- In patients with residual diuresis, renal clearance was the primary removal route for inulin (64.0%), beta2m (79.5%), and cystatin C (62.8%), while PD dominated urea removal (69.2%).
- Weekly solute removal indices (SRI) showed higher values for creatinine and inulin in non-anuric patients, indicating more efficient removal.
Conclusions:
- Solute removal during PD decreases as molecular weight increases.
- Anuric pediatric PD patients face a higher risk of accumulating middle molecules and small proteins.
- Further research is needed to determine the clinical impact and optimal threshold levels for removing middle molecules in PD patients.
Background:
Dialysis efficiency has a great influence on the outcome of patients. Few data are available on the removal of solutes with molecular weights higher than urea and creatinine. The aim of our study was to assess the transport and the removal of substances with molecular weights up to 15 kD and to evaluate the contribution of residual renal function in peritoneal dialysis (PD) children.
Methods:
Seventeen patients of 12 +/- 4 years undergoing automated PD were studied. Ten patients had 563 +/- 355 mL/day of urine output, and 7 were anuric. During a standardized nightly intermittent PD (NIPD) session, a single-injection inulin clearance was performed. Urea, creatinine, inulin (measured by HPLC), cystatin C and beta2-microglobulin (beta2m) were measured in blood, urine and dialysate. Clearances (L/week/1.73 m2) and weekly solute removal index (SRI) were calculated for all the solutes; weekly Kt/V was calculated for urea.
Results:
In non-anuric versus anuric patients the total clearances were: urea 82.6 +/- 18.3 versus 71.3 +/- 26.4; creatinine 82.7 +/- 28.6 versus 47.8 +/- 18.8; inulin 42.8 +/- 11.3 versus 32.8 +/- 20.4; beta2m 14.2 +/- 13.8 versus 9.2 +/- 8.3; cystatin C 20.2 +/- 9.4 versus 9.7 +/- 4.8. In the patients with residual diuresis, the urea was removed mainly by PD (69.2%), while inulin, beta2m and cystatin C were removed by renal clearance (64.0%, 79.5% and 62.8%, respectively). Total, peritoneal and renal weekly Kt/V values in the subjects with residual renal function, were 2.86 +/- 0.70, 1.99 +/- 0.40 and 0.87 +/- 0.43, respectively. Peritoneal weekly Kt/V in the anuric patients was 2.36 +/- 0.85; total weekly Kt/V in the total group was 2.65 +/- 0.78. Weekly SRIs in non-anuric versus anuric patients were: urea 2.56 +/- 0.58 versus 2.09 +/- 0.74; creatinine 2.66 +/- 0.73 versus 1.46 +/- 0.56; inulin 2.36 +/- 0.92 versus 1.64 +/- 1.60; beta2m 1.26 +/- 1.10 versus 1.20 +/- 1.90; cystatin C 1.72 +/- 0.83 versus 1.58 +/- 1.62.
Conclusions:
Solutes removed during PD tend to decrease following an increase in molecular weight of the substance. Since anuric patients are at higher risk of middle molecule and small protein accumulation, more attention should be paid to the removal of middle molecules. Further studies should be undertaken to evaluate whether removing them has a clinical impact and to determine their threshold levels.