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  • Präsentation Robert-Bosch-Krankenhaus 1

    Elektrolytstörungen bei Tumorerkrankungen Mark Dominik Alscher

    Freitag, 20. September 13

  • prärenal

    • Exsikkose bei

    - unzureichender Flüssigkeits- zufuhr - Erbrechen/Diarrhoe - Hyperkalzämie → Polyurie • Thrombotische Mikroangio- pathie - nach Stammzelltransplantation - medikamentös Gemcitabin Mitomycin C • Hepatorenales Syndrom durch veno-okklusive Erkrankung nach Hochdosis-Chemotherapie und Stammzelltransplantation

    Abb. 3.43: Renale Beteiligung bei Tumorerkrankungen und Chemotherapie

    renal postrenal

    glomerulär tubulo- interstitiell

    • Sekundäre membranöse Glomerulopathie

    • Sekundäre Minimal Change- Glomerulopathie bei T-Zell- assoziierten lymphoprolifera- tiven Erkrankungen und Thymomen • Sekundäre fokal segmentale Glomerulosklerose - bei Plasmazellerkrankungen - und monoklonaler Gammo- pathie unklarer Signifikanz (MGUS) - unter Pamidronat-Therapie • AL-Amyloidose bei multiplem Mylelom • Leichtkettennephropathie

    • Akute Tubulusnekrose

    - toxisch (Sepsis) - medikamentös (Cisplatin) • renale Tumorinfiltration bei Lymphomen und Leukämien • Leichtkettennephropathie • Tubuläre Obstruktion - Myelomniere („Cast-Nephro- pathie“) - Tumorlysesyndrom → Urat-Nephropathie → Calcium-Phosphat- Ablagerungen

    • Obstruktion der ableiten-

    den Harnwege durch - sekundäre retroperito- neale Fibrose bei Tumorerkrankungen - Verlegung der Ureteren- mündung oder der Urethra bei Prostatakarzinom Uteruskarzinom Blasentumoren

    Freitag, 20. September 13

  • underdosing can lead to ineffective cancer treatment. Thus, because the CKD-ESRD population has a higher prevalence of cancer and the CKD-ESRD population is increasing, more precise dosing rec- ommendations for this population are needed.31

    One suggestion would be for the reg- ulatory agencies, such as the U.S. Food and Drug Administration and the Euro- peanMedicinesAgency, to encourage that essential data on renal and dialysis clear- ance on new chemotherapeutic agents be made available. Monitoring renal func- tion inpatients receiving chemotherapy is essential; however, using serum creati- nine in malnourished patients with can- cer can overestimate kidney function, thereby risking chemotoxicity. Further- more,monitoring nephrotoxicity byusing serum creatinine will delay the identifica- tion of kidney injury, especially in patients with normal baseline function and a large renal reserve. More reliable measures are to use GFR to ensure appropriate dosing based on actual kidney function and kidney injury biomarkers to ensure early detection of kidney injury.22

    Fluid-Electrolyte Abnormalities in Cancer Fluid and electrolytes abnormalities are extremely common in patients with can- cer receiving chemotherapy because of the associated nausea, vomiting, and diarrhea and effects of the underlying disease on the nephron. In a recent survey, hyponatremia was noted in near- ly 50% of hospitalized patients with cancer.32 Although syndrome of inap- propriate antidiuretic hormone due to tumor-associated ectopic antidiuretic hormone, chemotherapeutic agents, nausea, antidepressants, pain, or pain medications is a widely known cause of hyponatremia in patients with cancer, intravenous hydration used during che- motherapy is a frequent cause for wors- ening hyponatremia. Hyponatremia is associated with an increase in mortality in patients with cancer.32 Therapy for hy- ponatremia in patients with cancer is sim- ilar to that in noncancer settings, although in practice sodium chloride tablets are more frequently used than the imposition

    of strict fluid restriction. Hypokalemia is also common in patients with cancer, mostly because of reduced potassium in- take and excess gastrointestinal loss but occasionally because of endocrine tu- mors.33 Renal tubular injury can occur frommyeloma proteins and several drugs that are tubular toxins causing potassium wasting and hypokalemia.3,34 Steroids used as part of a chemotherapeutic regi- men can, through their mineralocorticoid effects, also cause hypokalemia. Unlike in the noncancer setting, hypomagnesemia is fairly common in patients with cancer, especially those receiving some of the above-mentioned tubular toxins. A major adverse effect of cetuximab that targets the epidermal growth factor receptor is the occurrence of reversible urinary magne- sium loss leading to hypomagnesemia, a finding that has helped to clarify the role of epidermal growth factor receptor in tu- bular magnesium transport.35,36 Treating hypomagnesemia in patients with cancer can be challenging and may occasionally require intravenous administration be- cause large doses of oral magnesium can provoke severe diarrhea.37

    Hypophosphatemia is more common than hyperphosphatemia in patients with cancer, but both can occur in the setting of several cytotoxic drugs. Uptake of phosphorus by rapidly growing tumors can occasionally cause hypophosphate- mia, whereas rapid breakdown of tumors with chemotherapy, exemplified by tu- mor lysis syndrome associated with Bur- kitt lymphoma treated with rituximab, can lead to severe hyperphosphatemia. Derangement in calcium homeostasis is fairlycommoninpatientswithcancer.Hy- percalcemia can be mediated by tumor- secreted parathyroid hormone–related protein or from tumor-induced osteolysis or excess calcitriol production.38 Tumors may also release cytokines that activate osteoclasts directly or through such medi- ators as granulocyte macrophage colony- stimulating factors.39 Availability of several drugs for treating hypercalcemia, including the potent bisphosphonates, has dramatically improved hypercalce- miamanagement in patients with cancer, but some of these drugs are associated with their own nephrotoxicity.40

    ONCONEPHROLOGY AS A POSSIBLE SUBSPECIALTY IN NEPHROLOGY

    Medical practice in the inpatient cancer setting presents an enormous opportu- nity for teaching medical students and fellows the fundamentals of nephrology. Given the assorted nephrologic prob- lems in patients with cancer (listed in Table 1) and their increasing frequency, the view among a number of nephrolo- gists working with patients with cancer is that onconephrology should be con- sidered a specialized area within ne- phrology. If such a consideration is valid, entering an onconephrology fellowship through an accredited academic nephrol- ogy program at comprehensive cancer care centers might follow the 2-year gen- eral nephrology fellowship training. A formalized training program would help transform onconephrology into a dis- tinct discipline within nephrology, sim- ilar to transplant nephrology; enhance the options in the specialty of nephrology

    Table 1. Common clinical issues related to nephrologic management in patients with cancer

    Volume depletion AKI Sepsis and septic shock Severe fluid and electrolytes derangements Severe acid-base disorders Hyponatremia Hypokalemia Hyperkalemia Hypercalcemia Renal toxicity of chemotherapeutic agents Renal toxicity of nonchemotherapeutic drug treatments

    Tumor lysis syndrome Myeloma-related kidney injury Tumor- or tumor treatment–related microangiopathies and GN

    Tumor- or tumor treatment–related nephrotic syndrome

    Stem cell transplant–associated acute and chronic kidney injuries

    Cancer-associated obstructive uropathies Modifications of dosing of chemotherapy in patients with CKD and ESRD who have cancer

    Management of nutrition and dialysis in patients with ESRD receiving cancer therapy

    28 Journal of the American Society of Nephrology J Am Soc Nephrol 24: 26–30, 2013

    SPECIAL ARTICLE www.jasn.org

    Onconephrology: The Latest Frontier in the War against Kidney Disease

    JASN 2013;24:26

    depletion, increased propensity to de- velop contrast nephropathy, tumor lysis syndrome, abnormal uric acid homeo- stasis, hypercalcemia, myeloma and myeloma kidney, direct parenchymal involvement of the tumor, intense chemo- therapy protocols often involving nephro- toxic drugs, stem cell transplants with immunosuppression leading to sepsis, veno-occlusive disease, graft versus host disease, thrombotic microangiopathy, and a variety of additional causes and mechanisms.16–23 Furthermore, cancer therapy is increasingly available to elderly patients, a subpopulation that is particularly vulnerable to nephrotoxic drugs and intravenous radiocontrast media.24

    The list of potentially nephrotoxic drugs used in patients with cancer, espe- cially after stem cell transplantation, is long, and often includes several well known unavoidable nephrotoxins, such as platinum compounds, methotrexate, anti-VEGF agents, calcineurin inhibitors, aminoglycosides, colistin, acyclovir, amphotericin, cidofovir, and bisphosho- nates.3 It is well known that several che- motherapeutic agents can lead to AKI, but what is less well known is that re- duced renal function (whether from the chemotherapeutic agents themselves or from other mechanisms, such as volume depletion) can initiate a vicious cycle (Figure 1). Kidney failure leads to higher systemic chemotherapeutic levels that produce severe systemic toxicity, often re- sulting in neutropenic sepsis, multiorgan failure, and death. Therefore, optimizing the renal status of the patient before che- motherapy, such as by correcting volume status, removing potential nephrotoxic agents, and taking precautionary mea- sures against tumor lysis, can reduce the chance for AKI and chemotoxicity risks.

    Patients receiving outpatient chemo- therapy a