Spectrum of kidney diseases in malignancy

1. Spectrum of kidney diseases in malignancy Ayman El-Sebaie, MRCP(UK) Head of Nephrology Dept., IMC

2. INTRODUCTION • Patients with malignancy are particularly vulnerable to development of renal abnormalities. • High percentage of cancer patients are candidates for aggressive chemotherapy or radiation therapy, or both.

3. INTRODUCTION • The administration of NSAIDs for analgesia in the cancer patient may lead to ARF by elimination of the prostaglandin-mediated intra renal vasodilatation.

4. INTRODUCTION • Para proteins generated by multiple myeloma and other lymphoid neoplasms may produce renal dysfunction . • Malignancy-induced metabolic abnormalities, such as hypercalcemia and hyperuricemia, may impair renal function.

5. INTRODUCTION • Extra renal malignancy may involve the kidney by producing obstruction of urine flow via extrinsic compression of the urinary tract. • This occurs most often with gynecologic and other pelvic neoplasm in women and with prostatic cancer in men.

6. CLINICAL SYNDROMES 1-Acute renal failure • Pre renal,Intrinsic,Post renal. 2-Chronic renal failure. 3-Tubular dysfunction with fluid and electrolyte disorders. 4-Hematuria and/or nephrotic syndrome.

7. CAUSES OF HEMATURIA AND/OR NEPHROTIC SYNDROME • Paraneoplastic glomerulonephritis • Membranous GN • Minimal change nephrotic syndrome • Crescentic GN • Membranoproliferative GN • Primary or metastatic renal cancer • Chemotherapy agents causing nephrotic syndrome • Mitomycin C • Gemcitabine

8. Paraneoplastic Glomerulopathy • Patients with the neoplastic diseases are exposed to continuous antigenemia, which stimulates antibody production and forms circulating immune complexes. Semin Nephrol 1993,13:258–272. • Membranous nephropathy appears to be the most common glomerular lesion in patients with solid tumors.

9. Paraneoplastic Glomerulopathy • Minimal change glomerulopathy is another major form of glomerular disease associated with lymphomas, particularly with Hodgkin's disease.

10. TUMOR LYSIS SYNDROME • Occurs in malignancies that are highly proliferative and have high tumor burdens, such as lymphomas and leukemias. • Metabolic abnormalities—including hyperphosphatemia, hyperkalemia, hyperuricemia and/or hypocalcemia, and renal dysfunction. • Often, hyperuricemia (uric acid level ≥8 mg/dL) is a hallmark finding of tumor lysis syndrome.

11. TUMOR LYSIS SYNDROME A. Patients presenting (before chemotherapy) with evidence of large, rapidly proliferating tumor burden and hyperuricemia Prophylaxix: • 1. Correct initial electrolyte and fluid imbalance, and azotemia, if possible; dialysis as indicated for established renal failure or unresponsive electrolyte or metabolic abnormalities.

12. TUMOR LYSIS SYNDROME • 2. Maintain adequate hydration and urine output (>3 L/d). May require 4 to 5 L/24 h of intravenous hypotonic saline . • 3. Give Allopurinol* (300 mg/m2) at least 3 days before therapy if possible. • 4. Alkalinize urine to pH >7.0 (hypotonic NaHCO3 infusion; Diamox if necessary)

13. TUMOR LYSIS SYNDROME • 5. Postpone chemotherapy (if possible) until uric acid and electrolytes are reasonably normalized • 6. Continuous-flow leukapheresis might be indicated for patients with a high circulating blast count especially CML & AML.

14. TUMOR LYSIS SYNDROME • B. Patients presenting (before chemotherapy) with normouricemia, but still at risk • 1. Allopurinol* 300 mg/m2; at least 2 days before therapy if possible • 2. 4 to 5 L/d of intravenous fluids. • 3. Urinary alkalinization.

15. TUMOR LYSIS SYNDROME • C. Patients presenting (usually after chemotherapy) with renal failure • Same as for patients with tumor and hyperuricemia if sufficient renal function remains. • If dialysis is necessary,continuous hemodialysis or hemofiltration may be preferable if severe hyperuricemia or hyperkalemia is present

16. TUMOR LYSIS SYNDROME • Spontaneous or treatment-induced tumor lysis syndrome (TLS) can cause significant morbidity and potential mortality. • Vigorous hydration, alkalinization and inhibition of uric acid synthesis with allopurinol are the most frequently used methods for treatment and prevention of TLS.

17. TUMOR LYSIS SYNDROME • However, this approach fails to prevent renal insufficiency in up to 25% of high-risk patients. • Unlike allopurinol, urate oxidase promptly reduces the existing uric acid pool, prevents accumulation of xanthine and hypoxanthine and does not require alkalinization, facilitating phosphorus excretion.

18. TUMOR LYSIS SYNDROME • A recombinant form of urate oxidase, Rasburicase, is now registered for the treatment and prevention of TLS. Expert Rev Anticancer Ther. 2007 Feb;7(2):233-9.

19. HEMOLYTIC UREMIC SYNDROME • HUS is a thrombotic microangiopathy presenting as an acute illness characterized by renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. • Vascular and endothelial cell injury leads to microvascular thrombosis and ischemic organ damage. • HUS has been reported after chemotherapy for cancer.

20. HEMOLYTIC UREMIC SYNDROME • HUS can occur in diverse clinical settings, including metastatic carcinoma, particularly of the stomach, breast, or lung . • The initiating factor is presumably tumor emboli. • These patients have an extremely poor prognosis and often die within a few weeks of diagnosis.

23. Renal involvement in lymphoma. • Although primary renal lymphoma is rare, 5% to 10% of patients with disseminated lymphoma exhibit clinically detectable renal involvement. • At autopsy, the incidence of renal involvement by lymphoma has been estimated by several series to be more than 30% . • J Am Soc Nephrol 1997, 8:1348–1354.

24. Renal involvement in lymphoma • The incidence was higher in patients with lymphosarcoma or histiocytic lymphoma than in those having Hodgkin’s disease, with its occurrence in mycosis fungoides being intermediate in frequency. • The majority of patients had involvement of both kidneys. • Lymphoma may involve the kidney by multinodular or diffuse infiltration

25. Renal involvement In Leukemia • Renal infiltration occurs in approximately 50 per cent of patients with leukaemia. • Infiltration of the kidney is most often asymptomatic, only 13.5% of patients may present with flank pain & hematuria. • Although all types of leukemia may infiltrate the kidney, this most commonly occurs with lymphoblastic leukemia (83% in one study), when it is usually bilateral and diffuse throughout the cortex .

26. Renal involvement In Leukemia • The presence of large kidneys without hydronephrosis on U/S in a patient with lymphoma or leukemia, is highly suggestive of tumor infiltration. • The renal prognosis is dependent on the responsiveness of the tumor to radiation or chemotherapy. • A rapid reduction in renal size and return of renal function toward the baseline level may be seen within a few days with responsive tumors.

27. (A) Contrast-enhanced CT of the abdomen. Note the symmetrical, bilateral renal enlargement. The cortex of both kidneys is widened, the bipolar diameter of the kidneys amounts to 15 cm. • (B) CT of the abdomen in the same patient, after chemotherapy, 43 days later. A remarkable decrease in the size of both kidneys is seen. The widening of the cortex has disappeared. Note the subcapsular haematoma of the right kidney, caused by the renal biopsy.

28. Renal involvement In Leukemia • CLL may cause renal dysfunction in many different ways include: • uric-acid nephropathy (Tumor lysis syndrome). • light-chain nephropathy, • amyloidosis, • hypercalcaemia, • urinary obstruction, • glomerulonephritis, cryoglobulinaemia , • diffuse infiltration of leukaemic cells throughout the renal parenchyma (rare).

29. Radiation Nephritis • Acute form within 1 year • Chronic form within a decade. • Pathologically : interstitial fibrosis • Prevention: fractionate the dose,shielding and avoid nephrotoxic drugs.

30. Contrast Nephropathy • It is a relatively common cause of ARF in hospitalized patients. • Patients typically develop a rise in their serum Cr within 24 hours after the radio-contrast, sometimes with oliguria. • Renal failure is usually transient, although occasionally patients may require dialysis.

32. Contrast Nephropathy • Prevention: • Avoid unnecessary use of contrast studies. • High risk patients should be given saline Iv at a rate of 1 ml/kg/h beginning 12 hs before the procedure & 12 h afterwards. • Usage of non-ionic, low osmolality agents. • Avoid usage of other nephro-toxic drugs concomitantly.

33. MULTIPLE MYELOMA • In up to 25% of patients with multiple myeloma, ARF may be present at the time of initial diagnosis. • In others, it may occur at any time during the disease. • Renal failure can be due to diverse mechanisms.

34. MULTIPLE MYELOMA • Causes of ARF: • Light-chain cast nephropathy • AL amyloidosis • Light-chain deposition disease • Plasma cell infiltration of the kidney • Tubular dysfunction • Hypercalcemic nephropathy • Acute uric acid nephropathy • Radiocontrast nephropathy

36. MYELOMA KIDNEY

37. BMT Nephropathy • During the period of conditioning, tumor-lysis syndrome and stored marrow-infusion toxicity are most common. • 10 to 28 days after transplantation, the peak incidence of ARF is observed, most notably due to a hepatorenal-like syndrome associated with veno-occlusive disease (VOD).

38. BMT Nephropathy • After 1 month, the hemolytic-uremic syndrome (HUS) can be observed. • The greatest risk for development of ARF occurs 10 to 21 days after BMT, with the usual cause at this time being pre renal acute renal failure due to hepatic veno-occlusive disease. • This causes a syndrome very similar to the hepato-renal syndrome (HRS).

39. BMT Nephropathy • clinical similarities between the two syndromes: 1) jaundice and portal hypertension precede the onset of ARF. 2) a very low fractional excretion of sodium . 3) the blood urea nitrogen (BUN)/creatinine ratio is very high. 4) mild hyponatremia and a decrease in systemic arterial blood pressure are usually present,.

40. MESSAGES • Good Collaboration between the Oncologist and Niphrologist is paramount. • Early referral of renal impaired patients is crucial. • Cautious adjustment of drugs especially to old patient with malignancy.

41. MESSAGES • Avoid unnecessary use of contrast media and follow the protocol for patients at risk. • Close follow up to high risk cancer patients who receiving nephrotoxic drugs by serum Cr, electrolytes and fluid chart.

42. Thank You For Your Attention