Renal disease in systemic sclerosis (SS, scleroderma), and scleroderma renal crisis (SRC).

Renal disease in systemic sclerosis (SS, scleroderma), and scleroderma renal crisis (SRC).

Renal disease in systemic sclerosis (SS, scleroderma), and scleroderma renal crisis (SRC).

 

Almost 50 % of SS ptns may experience clinical evidence of kidney dysfunction, e.g. mild proteinuria, increased SCr, or HT. Renal dysfunction may be a collected reflection of prerenal failure, direct drug intoxication, impact of chronic HT, and, rarely, GN. Frequently, the renal alteration are unrelated to SS. On the other hand, SRC can be observed in in 5-20 % of SS ptns, mostly observed within 48 mo of Dgx and in those with diffuse cutaneous SS. It’s characterized by AKI, sudden onset of moderate to severe HT, a normal urinalysis or a urine sediment with mild proteinuria & few cells or casts, and/or Sns of MAHA (microangiopathic haemolytic anemia). It’s worthy to mention that 10 % of SRC ptns are normotensive. 

The histologic criteria in the kidney biopsy in SRC is intimal proliferation + thickening > narrowed + obliterated vascular lumen > concentric "onion-skin" hypertrophy. These alterations are indistinguishable from those in malignant hypertension. Risk factors for SRC may include:

1)    Steroid administration,

2)    Use of CyA (cyclosporine).

3)    Presence of palpable tendon friction rub,

4)    Autoantibodies against RNA polymerase,

5)    Early presentation with diffuse & advancing cutaneous affection.

Dgx of SRC is primarily based upon criteria in high-risk ptns with SSc that include new onset of BP >150/85 mmHg + progressive decline in kidney function, despite the finding of a few ptns are normotensive. More findings may include MAHA & thrombo-cytopenia, acute retinal findings related to malignant HT, new-onset proteinuria or haematuria. Kidney biopsy can be helpful in anticipating the persistence of RF. SRC must be DD from other types of TMA (thrombotic microangiopathy), especially TTP (thrombotic thrombocytopenic purpura) & HUS (Hemolytic-uremic syndrome). To allow proper initiation of ttt of SRC, close monitoring of all ptns with SS as follows:

v  In High-risk ptns (early-stage diffuse cutaneous lesions, rapidly progressive skin affection & palpable tendon friction rub) > daily home BP monitoring, biweekly for others.

v  Plasma Cr & dipstick testing for proteins or urinary protein-to-Cr ratio on a random 1^st morning urine sample on a 3-monthly basis.

 

There’s a little evidence concerned to avoiding and/or administration of any agent related to lowering the incidence of SRC. If steroid use is unavoidable in SS ptns, prednisone dosage should be limited to <15 mg/d for the shortest possible period. We do not generally use ACEi for to prevent the occurrence of SRC.  The therapeutic approach to the ptn with SRC varies with the ptn's BP and whether the ptn showed CNS manifestations or not. The following approach has been suggested:

(1)  The main target of initial captopril therapy is to bring the ptn to his/her previous baseline BP within 72 hs. As HT is acute in SRC, rapid BP decline to baseline does not usually simulate the risk expected with rapid BP decline in long-standing HT. However, some experts recommend maximum BP reduction of 20 mmHg/d.

(2)  In SRC, ACEi instead of other anti-HT drugs is recommended. The initial captopril therapy rather than other ACEi is advised owing to extensive clinical experience and its short onset & duration of action, permitting rapid dose escalation.

(3)  HT ptns with no evidence of CNS affection (e.g., encephalopathy, papilledema), 6.25-12.5 mg captopril is advised. Dose increments: 12.5-25 mg at 4-8-h intervals until target BP is reached. Maximum captopril dose is 300-450 mg/d.

(4)  HT ptns with CNS affection, the same captopril regimen can be given, for acute BP control, IV nitroprusside can be added. The latter should be withdrawn as soon as possible as captopril in increasing dosages can control the BP.

(5)  Normotensive ptns, start captopril at 6.25 mg, if tolerated, dose rising to 12.5 mg can be attempted. Further increments can be tried carefully to prevent hypotension.

 

Adding to BPcontrol, other parameters that can be monitored: platelet count, HB, haptoglobin & s. LDH. Despite ACEi therapy, almost 20-50 % of ptns with SRC may progress to ESRD. However, among ptns with SRC who requiring DX with their acute episodes, a considerable percent may recover sufficient kidney function to hold DX over a duration of up to 18 mo. Based primarily  upon survival benefits of KTx among all ptns with ESRD, KTx rather than HDX or PD maintenance among these ptns requiring RRT is currently advised. KTx is better postponed for at least 6 mo after commencing DX, to give a sufficient time for kidney function recovery.

 

References:

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Affiliations PMID: 12905479  DOI: 10.1002/art.11073

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[4] Steen VD, Syzd A, Johnson JP, Greenberg A and Medsger TA Jr. Kidney disease other than renal crisis in patients with diffuse scleroderma. J. Rheumatol 2005; 32, 649–655 PMID: 15801020

 

[5] Denton CP. Renal manifestations of systemic sclerosis—clinical features and outcome assessment. Rheumatology, 2008; 47 (Suppl. 5), v54–v56. https://doi.org/10.1093/rheumatology/ken307

[6] Caron M, Hudson M, Baron M, Nessim S, Steele R, Canadian Scleroderma Research Group Collaborators. Longitudinal study of renal function in systemic sclerosis J Rheumatol 2012; 39, 1829–1834. PMID: 22859351 DOI: 10.3899/jrheum.111417

 

[7] Hudson M, Baron M, Tatibouet S, Furst DE, Khanna D, International Scleroderma Renal Crisis Study Investigators. Exposure to ACE inhibitors prior to the onset of scleroderma renal crisis-results from the International Scleroderma Renal Crisis Survey. Semin. Arthritis Rheum 2014; 43, 666–672. https://doi.org/10.1016/j.semarthrit.2013.09.008