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Lack of activation of renal functional reserve predicts the risk of significant renal involvement in systemic sclerosis
  1. Riccardo Livi1,
  2. Serena Guiducci2,
  3. Federico Perfetto1,
  4. Gabriele Ciuti1,
  5. Elisa Grifoni1,
  6. Letizia Conforti2,
  7. Felice Galluccio2,
  8. Alberto Moggi Pignone1,
  9. Marco Matucci Cerinic2
  1. 1Department of Internal Medicine, University of Florence, Florence, Italy
  2. 2Department of Medicine and Biomedicine, Division of Rheumatology AOU Careggi, University of Florence, Florence, Italy
  1. Correspondence to Riccardo Livi, Department of Internal Medicine, University of Florence, Viale Pieraccini 18, I-50139 Firenze, Italy; rlivi{at}


Objective To evaluate if defective activation of renal functional reserve (RFR) in systemic sclerosis (SSc) without clinical signs of renal involvement predicts the risk of developing clinically relevant renal damage.

Methods Twenty-eight normotensive SSc patients with normal renal function and no urinary abnormalities were submitted to an intravenous amino acid load to activate RFR. Nineteen patients (six with diffuse cutaneous SSc (dcSSc)) had an RFR activation defect, while nine (two with dcSSc) showed normal RFR. All patients were followed up for 5 years, with periodic evaluation of renal function, urinary protein excretion and systemic blood pressure (BP).

Results At admission, patients with normal RFR had lower BP than those with abnormal RFR; no age, disease duration or creatinine clearance (CCr) differences were found. Five years later, patients with abnormal RFR showed, with respect to basal values, a significantly higher CCr reduction than patients with normal RFR (mean percent decrease 15.4±9.5 vs 2.6±3.8, p<0.001). Among patients with abnormal RFR, 13 (68.4%) showed a CCr reduction of ≥2 ml/min/year, with a final CCr of ≤70 ml/min in eight cases; two patients developed microalbuminuria and 10 grade 1 or 2 systemic hypertension. Significant CCr reduction rates were found in eight patients with high BP and in five patients who remained normotensive. No patient with normal RFR had proteinuria or high BP during follow-up.

Conclusions Lack of RFR activation is an early sign of renal involvement in SSc, and is a harbinger of an increased risk of developing renal insufficiency and systemic hypertension.

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  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.