What are the guideline and inclusion criteria for a research study on the correlation between appendicular lean mass index (ALMI) and chronic kidney disease (CKD) stage in diabetic nephropathy patients?

Research Study Design: ALMI and CKD Stage Correlation in Diabetic Nephropathy

Study Population and Inclusion Criteria

Primary Inclusion Criteria:

• Adults aged ≥18 years with type 2 diabetes mellitus and biopsy-proven or clinically diagnosed diabetic nephropathy 1
• CKD stages 3-5 (eGFR 15-59 mL/min/1.73 m²) confirmed by two measurements at least 3 months apart 1
• Albuminuria present (UACR ≥30 mg/g) documented on at least 2 of 3 specimens collected over 3-6 months 1
• Stable kidney function defined as <30% change in serum creatinine over the preceding 3 months 1

Specific CKD Stage Stratification:

• Stage 3a: eGFR 45-59 mL/min/1.73 m² 1
• Stage 3b: eGFR 30-44 mL/min/1.73 m² 1
• Stage 4: eGFR 15-29 mL/min/1.73 m² 1
• Stage 5: eGFR <15 mL/min/1.73 m² (not yet on dialysis) 1

Body Composition Assessment Requirements:

• Participants must be able to undergo dual-energy X-ray absorptiometry (DEXA) scanning for accurate appendicular skeletal muscle mass measurement 2, 3
• Alternatively, bioimpedance spectroscopy (BIS) with Body Composition Monitor (BCM) using Lin's algorithm for ASM estimation is acceptable 4, 3
• Minimum weight 40 kg and maximum weight 200 kg to accommodate DEXA scanner limitations 2

Exclusion Criteria

Absolute Exclusions:

• Patients currently receiving any form of renal replacement therapy (hemodialysis, peritoneal dialysis, or kidney transplantation) 1
• Type 1 diabetes mellitus 1
• Polycystic kidney disease or other rare kidney diseases (>150 conditions as defined by KDIGO) 1
• Active malignancy or history of malignancy within the past 5 years (except non-melanoma skin cancer) 1
• Acute kidney injury within the preceding 3 months defined as ≥50% increase in serum creatinine 1
• Pregnancy or breastfeeding 5

Clinical Exclusions:

• Severe heart failure (NYHA class IV) with fluid overload that would confound body composition measurements 1
• Active systemic infection or inflammatory disease requiring treatment within the past 4 weeks 4
• Limb amputation that would affect appendicular skeletal muscle mass measurement 2
• Inability to lie flat for DEXA scanning or contraindications to BIS measurement (pacemaker, implantable cardioverter-defibrillator) 2, 4
• Severe malnutrition defined by Protein Energy Nutrition Status criteria (serum albumin <3.0 g/dL with evidence of inadequate intake) 1

Medication-Related Exclusions:

• Use of systemic corticosteroids (>10 mg prednisone equivalent daily) for >2 weeks within the past 3 months 4
• Recent initiation (<3 months) of SGLT2 inhibitors, as these cause transient eGFR changes that could confound CKD staging 1, 5

Primary Outcome Measures

Appendicular Lean Mass Index (ALMI) Definition:

• ALMI calculated as appendicular skeletal muscle mass (kg) divided by height squared (m²) 2, 3
• Low ALMI defined as <10% of age- and sex-specific normal values 4
• Sarcopenia defined as low ALMI combined with low muscle strength (handgrip strength <26 kg for men, <18 kg for women) 2

CKD Stage Assessment:

• eGFR calculated using the CKD-EPI 2021 equation without race adjustment 1
• Confirmation of CKD stage by measuring iohexol clearance or other gold-standard GFR measurement in a subset of participants 2
• Albuminuria category assignment: A1 (<30 mg/g), A2 (30-300 mg/g), A3 (>300 mg/g) 1

Secondary Outcome Measures and Covariates

Nutritional Assessment:

• Comprehensive nutritional assessment using Subjective Global Assessment (SGA) 7-point scale at baseline 1
• Serum albumin, prealbumin, and transferrin levels 1
• Dietary protein intake assessment via 3-day food diary (target 0.8 g/kg/day for CKD stages 3-5) 1, 6

Inflammatory Markers:

• High-sensitivity C-reactive protein (hs-CRP) 1, 4
• Interleukin-6 and tumor necrosis factor-α levels 4

Metabolic Parameters:

• HbA1c with target <7.0% per KDOQI guidelines 1
• Fasting glucose, lipid panel (LDL-C, HDL-C, triglycerides) 1
• Serum creatinine, blood urea nitrogen, electrolytes (sodium, potassium, bicarbonate) 1

Physical Function Assessment:

• Handgrip strength measurement using dynamometer 2
• Isometric quadriceps strength testing 2
• Berg Balance Scale and functional reach test 2

Body Composition Variables:

• Total lean tissue mass (LTM) and lean tissue index (LTI = LTM/height²) 4, 3
• Fat mass and fat tissue index (FTI = fat mass/height²) 4, 3
• Body mass index (BMI) with stratification: normal (18.5-22.9 kg/m²), overweight (23-24.9 kg/m²), obese (≥25 kg/m²) for Asian populations 7, 8

Sample Size and Statistical Considerations

Minimum Sample Size:

• Based on prior studies showing significant associations between muscle mass and GFR, a minimum of 150 participants is required to detect a correlation coefficient of r=0.3 with 80% power and α=0.05 2, 3
• Stratify enrollment to ensure at least 30 participants per CKD stage (stages 3a, 3b, 4, and 5) 2

Statistical Analysis Plan:

• Linear regression analysis with stepwise method to assess the relationship between ALMI (dependent variable) and CKD stage (independent variable) while adjusting for age, sex, diabetes duration, HbA1c, BMI, and inflammatory markers 2, 4, 3
• Multivariate Cox regression analysis if longitudinal follow-up is included to assess progression to renal replacement therapy or 50% decline in eGFR 7, 8
• Subgroup analyses stratified by sex, as men demonstrate higher rates of sarcopenia (44% vs 22% in women) in CKD populations 2

Monitoring and Follow-Up Schedule

Baseline Assessment:

• Complete medical history including diabetes duration, comorbidities (cardiovascular disease, hypertension), and current medications 1
• Physical examination with blood pressure measurement (target <130/80 mmHg per KDOQI guidelines) 1, 6
• Laboratory testing: serum creatinine, eGFR, UACR, complete metabolic panel, HbA1c, lipid panel, albumin, hemoglobin, inflammatory markers 1
• Body composition assessment via DEXA or BIS 2, 4, 3
• Nutritional assessment using SGA 7-point scale 1
• Physical function testing (handgrip strength, quadriceps strength, balance tests) 2

Follow-Up Intervals (if longitudinal component included):

• Repeat eGFR and UACR every 3-4 months for CKD stages 4-5 or UACR ≥300 mg/g 6, 9
• Repeat eGFR and UACR every 6 months for CKD stage 3 with UACR 30-299 mg/g 6, 9
• Repeat body composition assessment every 6 months 2, 4
• HbA1c monitoring every 3 months until target achieved, then every 6 months 1, 6

Quality Control and Standardization

Laboratory Standardization:

• Use internationally standardized methods for serum creatinine measurement (IDMS-traceable) 1
• Albumin measurement standardized to international reference standards 1
• All laboratory measurements performed at a single central laboratory to minimize inter-laboratory variation 1

Body Composition Measurement Standardization:

• DEXA scans performed on the same machine by trained technicians using standardized protocols 2
• BIS measurements performed in the supine position after 10 minutes of rest, with participants fasting for at least 4 hours and having emptied their bladder 4, 3
• Calibration of equipment performed weekly per manufacturer specifications 2, 4

Data Collection and Management:

• Electronic case report forms with built-in range checks and logic validation 1
• Regular monitoring visits to ensure protocol adherence and data quality 1
• Independent data safety monitoring board for longitudinal studies 1