This document provides information on rapidly progressive renal failure (RPRF), including its definition, causes, investigations, diagnosis, and treatment. Key points: - RPRF is characterized by progressive renal failure over weeks that is not due to acute kidney injury or chronic kidney disease. The kidney biopsy often shows lesions in the glomerular, tubulointerstitial, or vascular compartments. - Common causes of RPRF include crescentic glomerulonephritis (seen in 54% of cases), acute interstitial nephritis (18%), and IgA nephropathy (15%). - Diagnosis involves ruling out other causes through history, physical exam, labs, and

1. RPRF

2. Concept
• Progressive renal failure over a period of few weeks of seemingly unknown
etiology
• Neither AKI nor CKD
• Normal sized kidneys
• The renal histopathology shows lesions affecting any or a combination of the
three traditional renal compartments: glomerular, tubulointerstitial or vascular.
• Since a wide variety of different diseases may present with a similar clinical
picture, it is essential to properly work-up cases of RPRF so that the exact
diagnosis is established.
• Time is a valuable factor since if the appropriate treatment is not initiated, then
the patient may progress to irreversible ESRD needing life-long renal replacement
therapy.
• RPRF may in fact be considered as ‘Renal Emergency’.

3. History
• Exclude CKD or AKI by history
• History of
• Hematuria,
• Hemoptysis, s/o Vasculitis
• Longstanding asthma
• Petechiae
• Arthralgia,
• Oral ulcers s/o Lupus
• Photosensitivity
• Back ache
• Bone pains s/o Myeloma
• Previous medical records
• History of diabetes and
hypertension

4. Physical examination
• Absence of pallor is one of the signs that may suggest RPRF.
• In general, patients with RPRF have normal BP.
• However hypertension is a feature in patients with underlying TMA and renal
artery stenosis.
• Finding of oral ulcer or butterfly rash is indicative of lupus,
• Skin petechiae may indicate lupus or vasculitis.

5. Causes of RPRF

6. Investigations
• Impaired renal functions in a patient with short history (2 weeks – 3 months).
• The most important investigation which suggests the diagnosis of RPRF is the
presence of normal sized kidneys on ultrasonographic examination of the
abdomen.
• Urine examination
• Active urinary sediment (proteinuria, dysmorphic RBCs and RBC casts) suggests proliferative
glomerulonephritis,
• Hematuria with isomorphic RBCs is indicative of acute interstitial nephritis

7. Renal biopsy
Most cases of RPRF need a renal biopsy either to
make the correct diagnosis or to understand the
chronicity of the disease process

8. Distribution of various histologic entities
CRESCENTIC GN
54%
AIN
18%
IgA
15%
ATN
8%
OTHERS
5%
CRESCENTIC GN
AIN
IgA
ATN
OTHERS

9. RPGN

10. Crescentic GN
• Characterised clinically by rapid loss of renal function, and pathologically by
extensive crescents often with necrosis of the glomerular tuft.
• A crescent forms as a result of the proliferation of the glomerular epithelial cells
resulting in compression of the glomerular tuft.
• Crescentic glomerulonephritis occurs in the
• Various forms of vasculitis (both primary renal and systemic);
• PIGN,
• Lupus nephritis,
• IgA nephropathy and
• Membrano-proliferative glomerulonephritis.

11. Clinical features
• Clinical features of RPGN may consist of cola-coloured urine, generalized non-
specific constitutional symptoms or a flu-like syndrome.
• Blood pressure is normal or only slightly raised.
• Purpura may be present.
• Signs and symptoms of the underlying disease may be present, and provide a clue
to the diagnosis.
• A small but significant percentage of patients may be asymptomatic.

12. Labs
• The two important tests, which help in the differential diagnosis of RPGN are
• Serum Antineutrophilic Cytoplasmic antibody (ANCA), which is of two types
• p-ANCA (directed against myeloperoxidase) and
• c-ANCA (directed against PR3);
• Immunofluorescence (IF) examination of the kidney biopsy.

13. Types
• The disease can be primary or secondary. Primary or idiopathic crescentic
glomerulonephritis is classified into the following types:
• Type 1 (anti-glomerular basement membrane [GBM] disease) presents with linear
deposits of immunoglobulin G (IgG)
• Type 2 (immune-complex mediated) presents with granular deposits of
immunoglobulin
• Type 3 (pauci-immune) presents with few or no immune deposits, antineutrophil
cytoplasmic antibody-associated small vessel vasculitis (SVV) that may be renal-
limited or part of a systemic disease, for example, granulomatosis with polyangiitis
(GPA).
• Type 4 includes combinations of types 1 and 3
• Type 5 is ANCA-negative, pauci-immune renal vasculitis (5% to 10% of cases)

14. Diagnosis

15. Treatment
• Untreated RPGN typically progresses to end-stage renal disease over a period of
weeks to a few months. However, patients with fewer crescents (<50 percent of
glomeruli affected by crescents on initial biopsy) may have a more protracted, not
so rapidly progressive course
• Supportive therapy involves control of infection (especially Pneumocystis jiroveci
(PCP) infection with trimethoprim-sulfamethoxazole or atovaquone), control of
volume status (providing dialysis if required), and smoking cessation.

16. Specific therapy- induction of remission
• The initial therapy is to induce remission which typically consists of
glucocorticoids and cyclophosphamide administration, which induces 85% to 90%
of patients in 2 to 6 months, with about 75% achieving complete remission.
• Recently, rituximab proved a comparable substitution for cyclophosphamide in
RAVE and RITUXIVAS trials, and it may be used in patients who cannot take or
refuse to take cyclophosphamide.
• At present, the mainstay of therapy remains cyclophosphamide and steroids for
induction of remission, with an option to consider rituximab in select patients.

17. Specific therapy- induction of remission
• Plasma exchange is useful in patients with
• Advanced renal failure (serum creatinine greater than 5.6 mg/dl or requiring dialysis),
• Severe pulmonary hemorrhage, and
• Anti-glomerular basement membrane antibody disease.
• Although short-term results with plasma exchange are encouraging, the long-
term benefits remain unclear, and the PEXIVAS (Plasma Exchange in Vasculitis)
trial finding showed no benefit of Plasma exchange in patients with ANCA
vasculitis.

18. Specific therapy-maintenance of remission
• It is important to prevent relapse, as relapses are common, especially in
granulomatosis with polyangiitis and microscopic polyangiitis.
• Continue with immunosuppressive therapy, using less toxic agents, to maintain
remission and to prevent relapse.
• Either azathioprine or methotrexate usually is used for maintenance therapy to
reduce the risk of relapse.
• In a recent study by the French Vasculitis Study Group in the MAINRISTAN trial,
rituximab 500 mg every 6 months showed an exceptional reduction in the relapse
rate with rituximab versus azathioprine at 28 months (5% versus 25%).

19. Poor prognostic factors
• Crescents in more than 80% of glomeruli, especially circumferential fibrocellular
or fibrous/acellular crescents
• Initial serum creatinine level of more than 5.6 mg/dL or glomerular filtration rate
of less than 5 mL/min at presentation
• Oliguria
• Presence of anti-GBM antibody
• Age greater than 60 years

20. Other causes

21. Lupus nephritis
• Diagnosed on kidney biopsy + positive serology.
• IF examination showing deposition of IgG, IgM, IgA, C3 and fibrinogen (full-hose
deposition) is highly suggestive of lupus nephritis.
• 5 classes based primarily on the glomerular involvement. However it also involves
the interstitium and renal blood vessels in varying degrees.
• RPRF occurs mainly in two groups of patients:
• Lupus nephritis class IV
• Diffuse endocapillary proliferative glomerulonephritis (DPGN)
• Necrotising crescentic glomerulonephritis
• Thrombotic microangiopathy as a result of lupus nephritis (APLA may be present)
• Kidney biopsy is mandatory in lupus patients with active urinary sediment.
• Delay in diagnosis results in irreversible loss of renal function.

22. Thrombotic Microangiopathy
• TMA affects arterioles and glomerular capillaries.
• The important causes of TMA include
• Shiga-toxin induced HUS,
• TTP due to ADAMTS13 deficiency,
• pregnancy,
• Antiphospholipid antibody syndrome,
• systemic sclerosis,
• malignant hypertension
• certain drugs.

23. Thrombotic Microangiopathy
• The histologic lesions of arteriolar type of TMA consist of
• Myointimal proliferation,
• Reduplication of the lamina elastica
• Intraluminal platelet thrombi resulting in partial or total obstruction of the vessel lumen.
• The glomeruli, when affected, show thrombi in the capillary loops and
mesangiolysis.
• TMA is suspected on the basis of
• History,
• Thrombocytopenia and
• Evidence of microangiopathic hemolytic anemia (peripheral smear showing fragmented RBCs
and raised serum LDH).

24. Multiple Myeloma
• High index of suspicion is needed especially if investigations reveal
• Hypercalcemia
• Renal impairment,
• Hyperuricemia and
• Raised serum globulins.
• The diagnosis is made by serum and urine protein electrophoresis, and bone
marrow examination
• Early diagnosis and institution of treatment may reverse the renal failure.

25. Thrombo-Embolic Disease
• Atheromatous renal artery stenosis and cholesterol embolisation to the kidney
are often associated, and are a cause of ischemic renal disease leading to
subacute renal failure.
• Thrombo-embolic renal disease occurs as a result of cholesterol embolism after
manipulation of the aorta: angiography, angioplasty and vascular surgery.
• Occasionally it may occur spontaneously in patients with extensive
atherosclerosis.
• On kidney biopsy cholesterol clefts are seen in medium sized vessels with giant
cell reaction and re-canalisation

26. Other causes
Acute Interstitial Nephritis
• The clinical presentation of AIN
• may be like RPRF or sometimes even
AKI.
• About half of all cases of AIN are
caused by drugs.
• The other causes include various
infections, malignancies and
sarcoidosis.
Acute Tubular Necrosis
• Although ATN usually presents
abruptly, on rare occasions renal
biopsy of a suspected RPRF case
reveals ATN.

27. Thank you