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An elderly suffering from acute renal failure

An elderly suffering from acute renal failure. Speaker: Dr C W Chow Chairperson: Dr W T Wong Intensive Care Unit Caritas Medical Centre 24 th July 2012. Our Patient. M/79 Hypertension Old cerebrovascular accident, CT brain: left internal capsule old infarct

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An elderly suffering from acute renal failure

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  1. An elderly suffering from acute renal failure Speaker: Dr C W Chow Chairperson: Dr W T Wong Intensive Care Unit Caritas Medical Centre 24th July 2012

  2. Our Patient • M/79 • Hypertension • Old cerebrovascular accident, CT brain: left internal capsule old infarct • Benign Prostatic hypertrophy • First presented to CMC Medical Clinic in Dec 2008 for renal impairment.

  3. History of multiple myeloma • Renal impairment Ur: 8.2mmol/L Cr: 202umo/L • Normochromic Normocytic anaemia Hb: 7.6g/dL • Reverse A/G ratio Albumin 23g/L, Globulin 96g/L

  4. Previous work up for multiple myeloma • Serum electrophoresis and immunofixation Monoclonal IgG/Lambda detected. • IgG: 7070mg/dl (819-1725mg/dl) IgA: 24mg/dl (70-386mg/dl), IgM: 16mg/dl (55-307mg/dl) • BMA/Trephine Biopsy: Well differentiated myeloma cell content about 20% of all cells

  5. Treatment of multiple myeloma • 10 cycles of Melphalan and Prednisolone Every Cycle M&P for 5 days Melphalan 4mg daily Prednisolone 60mg daily • Treatment from 2/2009 to 3/2010

  6. This admission • Presented to medical ward for diarrhoea and decreased urine output on 6th September 2011. • Blood test found acute renal failure. • Transferred to ICU for acute renal failure and suspected myeloma kidney

  7. This admission

  8. Bone marrow aspiration and trephine biopsy result

  9. Progress • USG kidney confimred no evidence of obstructive uropathy. • Renal suggested to consider plasmapharesis. • Performed Renal Biopsy after stabilization • Transferred to ICU

  10. Progress • PMH Haematology consultation Started on dexamethasone 20mg daily on 16 September. Plan to transfer to PMH Haematology ward for chemotherapy with renal support in PMH.

  11. Deterioration • Develop severe abdominal pain with peritoneal sign on 17 September. • Surgical team consulted and urgent plain CT abd performed.

  12. Operative record • 1L blood stained peritoneal fluid • Fibrous band stemming from anti-mesenteric border of sigmoid colon attaching to left pelvic side wall leading to internal herniation and ischemia of small bowel. • 80cm full thickness infarct of small bowel • Small bowel resection and primary anastomosis

  13. Pathology report Small intestine pathology on 19 Sep Bone marrow smear and trephine biopsy on 14 Sep

  14. Progress • Gradual deterioration in renal function again after operation. • Decided to try High Cut off Haemodialysis with special large pore dialyser membrane rather than plasmapharesis with intermittent HD.

  15. Progress • Renal function remained static. • Dialysis independent. • Transferred to PMH Haematology on 30 September. • Completed consolidation chemotherapy with high dose dexamethasone and Bortezomib and discharge on 12 Oct

  16. Progress After finishing consolidation chemotherapy • IgG level down 14-25g/L • Hb level around 9g/dL • Cr static around 280umol/L Tholidomide as maintenance since Jan 2012 • IgG level remained low. • Cr static around 200umol/L

  17. High cut-off haemodialysis (HCO HD) in a patient with multiple myeloma

  18. Multiple Myeloma • Multiple myeloma is a cancer of plasma cells. • Intact immunoglobulin • Isolated clonal free light chain (FLC)

  19. Free Light Chain (FLC) • Accurate immunoassay found all myeloma patients have detectable free light chain secretion. • Serum FLC level depends on level of synthesis by plasma cells and clearance by kidney.

  20. Mechanism of myeloma kidney • Production of FLC in normal individual is approximately 500mg per day. • Rapidly cleared and metabolized by the kidney within the proximal tubules, half-life of 2-6 hours. • In myeloma patient, excessive synthesis of FLC occurs which overwhelm the absorption limit of proximal tubules Dimopoulos MA, Kastritis E, Rosinol L, Blade J, Ludwig H. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia 2008;22:1485-93

  21. Cast nephropathy • FLC enter the distal tubules causing cast formation and direct cellular damage. • Distal tubular casts and interstitial inflammation. • Tubular cast is formed by FLC and Tamm-Horsfall protein, a glycoprotein synthesized in medullary thick ascending limbs of loop of Henle Cockwell P, Hutchison CA. Management options for cast nephropathy in multiple myeloma. Curr Opin Nephrol Hypertens 2010;19:550-5

  22. Extracorporeal removal of FLC • Free light chain is the culprit of myeloma cast nephropathy. • Decrease in serum FLCs should lower renal exposure and slow renal tubular injury. • Direct removal of FLCs from the blood is a theoretical attractive treatment option. • Benefit will only be achieved in the presence of effective chemotherapy.

  23. Molecular size

  24. High Cut off dialysis • Cut off for conventional high flux dialyser in blood is around 10kD. • Cut off for HCO HD dialyser is around 45kD. • Cut off for plasmafilter is even bigger.

  25. High Cut off dialysis • Haemodialysis using conventional or high flux dialyser is ineffective for the removal of FLC due to the small pore size. • High cuff off dialyser membrane is characterized by very large pores, 3 times the size of a normal high flux filter. Gondouin B, Hutchison CA. High cut-off dialysis membranes: current uses and future potential. Adv Chronic Kidney Dis 2011;18:180-7.

  26. HCO dialyser membrane • HCO membranes offer significantly increased removal of molecules with molecular weights of 15 -60kDa as compared with conventional high flux membrane. • Pore size of HCO membrane is adequate for removal of free light chains Gondouin B, Hutchison CA. High cut-off dialysis membranes: current uses and future potential. Adv Chronic Kidney Dis 2011;18:180-7.

  27. Plasma exchange • Plasma exchange involve withdrawal of venous blood, separation of blood from plasma and reinfusion of cell plus plasma or replacement fluid. • Plasma and blood are separated by centrifugation or membrane filtration • Plasma exchange has been suggested for treatment of myeloma kidney by rapidly reducing the plasma concentration of myeloma protein.

  28. Plasma exchange • A randomised study in 1988 found patient treated with plasma exchange on top of steroid and cytotoxic therapy had benefit in renal recovery and survival. • Another small randomised trial found only more significant lowering of myeloma protein without significant benefit in renal recovery and survival.

  29. Plasma exchange • Failure of removal of free light chain by plasma exchange is due to the high extravascular distribution and synthetic rate. • PE of one plasma volume remove 65% of the intravascular compartment FLC. • FLC rapidly reequilibrates with the extravascular reservoir and only 13% of total body load of FLC removed. • Extended filtration is not possible for PE.

  30. HCO Dialysis vs Plasma exchange • Effective removal of FLC can be achieved by extended HD with HCO dialyser, up to 8hours per section. • Mathematical model showed that HCO HD is more effective than PE for removal of FLC. Hutchison CA, Cockwell P, Reid S, et al. Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol 2007;18:886-95.

  31. FLCs removal by HCO HD • Serum free kappa and lambda light chains are efficiently cleared by High Cut off HD. • Two dialyser in series can improve the efficiency of removal of FLCs. Hutchison CA, Cockwell P, Reid S, et al. Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol 2007;18:886-95.

  32. Renal recovery • Fourteen of the 19 patients who received FLC removal HD became independent of dialysis at a median of 28 d (range 13 to 120) Hutchison CA, Bradwell AR, Cook M, et al. Treatment of acute renal failure secondary to multiple myeloma with chemotherapy and extended high cut-off hemodialysis. Clin J Am Soc Nephrol 2009;4:745-54

  33. Renal recovery and FLCs removal • Renal recovery depends on early reduction of serum FLCs. • Renal recovery associates with survival advantage. Hutchison CA, Bradwell AR, Cook M, et al. Treatment of acute renal failure secondary to multiple myeloma with chemotherapy and extended high cut-off hemodialysis. Clin J Am Soc Nephrol 2009;4:745-54

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