Ann R. Shannon, B.A Kenneth Weizer, N.D. Stephen G. Chandler, M.D. Heather Zwickey, Ph.D.

Direct correspondence to:
Ann R. Shannon, B.A.1 Certified Jin Shin Jyutsu® Practitioner 7314 NE Foss Avenue Portland, OR 97204 ann_shannon@hotmail.com

A patient with recurrent myeloma (serum creatinine (SCr) 11.3 mg/dl) was diagnosed with end stage renal disease secondary to myeloma kidney. He sought complementary care for renal function recovery (RFR). Treatment and Outcome: Jin Shin Jyutsu®(JSJ), naturopathic renal supplements, and constitutional hydrotherapy were employed. Treatment increases addressed SCr spikes associated with uncontrolled myeloma. Dialysis was discontinued after 6 weeks (SCr, 2.0 mg/dl). Though UPE M-proteins rose to 10.4 g/day, all SCr spikes rapidly reduced after resuming discontinued supplements and hydrotherapy or increasing hydrotherapy and JSJ. Sufficient renal function allowed participation in a Velcade clinical trial. Remission was achieved and no further dialysis was required. Conclusions: The whole practice regimen is likely to have played a key role in allowing RFR. Additional reports are necessary to determine a general benefit. Future clinical trials should identify any specific role(s) played by treatment component(s) and whether the whole practice allows a synergistic effect.

Introduction

In multiple myeloma (MM), malignant bone marrow plasma cells overexpress immunologically impotent monoclonal proteins (M-proteins) (1). Up to 50% of MM patients eventually experience renal insufficiency associated with hypercalcemia or myeloma light chain deposition disease (2,3). Dehydration, infection, nephrotoxic drugs, recent surgery, contrast media (4), hyperviscosity and hyperuricemia (1) can also factor in renal failure. Reversibility of renal failure has been reported in 15%-58% of myeloma patients, most commonly in patients receiving prompt treatment who have slight to moderate renal damage, hypercalcemia and low M- protein excretion (3, 5). End stage renal disease (ESRD) in myeloma patients is associated with decreased survival. Effective treatment modalities for recovery of renal function would be a significant adjunct to care of patients with renal deficiency in general and myeloma kidney in particular.

Case History

On July 11, 2002, a 59 year old Caucasian male presented at the ER unable to urinate, with lower back pain and 38.3°C fever. The patient was on day 24 of his first regimen of vincristine, doxorubicin and dexamethasone (VAD) chemotherapy for recurrent, free kappa light chain MM (originally diagnosed December, 1999, stage IIB). Complete remission had ended when M-proteins by urinary protein electrophoresis (UPE) measured 1.9 g/day on May 23, 2002. UPE M-proteins were rising rapidly. (See Figure 1) Family history included multiple cancers, no MM or renal failure.

Laboratory studies revealed serum creatinine (SCr), 3.9 mg/dL (normal value (NV) .8-1.3 mg/dl); high blood urea nitrogen (BUN), 38 mg/dl (NV 9-25 mg/dl); normal serum calcium, 8.5 mg/dl (NV 8.4-10.2 mg/dl). The patient was hospitalized with acute renal failure secondary to MM. A port was placed and hemodialysis was initiated on July 13th with SCr at 9.6 mg/dl. End stage renal disease (ESRD) secondary to myeloma kidney was diagnosed when SCr reached 11.3 mg/dl, two days after dialysis began. The patient was counseled that renal failure was irreversible and dialysis would be permanent. Subsequently diagnosed Herpes zoster may have contributed to deterioration of renal status.

Treatment and Outcomes

The patient sought complementary care for renal function recovery (RFR). Jin Shin Jyutsu® (JSJ), a Japanese energetic healing art sharing ancient lineage with acupuncture and acupressure, was initiated. JSJ had been previously employed by the patient and reported upon (6). Four JSJ kidney flows and a spleen flow (7) were administered daily throughout hospitalization. Minimal ability to intermittently urinate (100-500 ml/day) returned before discharge to outpatient hemodialysis on July 17th. That evening, the patient voided 750 mls. He never experienced difficulty urinating again. After hospitalization, more comprehensive JSJ treatments (3/week) began. A second, dialysis-adjusted regimen of chemotherapy began on July 19th. On July 23rd, urine production had increased to >2000 ml/day; pre-dialysis laboratory studies measured: SCr, 7.6 mg/dl; pre-dialysis BUN, 64 mg/dl; creatinine clearance (CCr), 11.4 ml/min (NV, 97.0-137.0 ml/min). The dialysis nephrologist counseled that improvement was insignificant and that all ability to urinate would ultimately disappear.

The patient’s primary agenda at July 22nd initial naturopathic exam was RFR. Renal failure and MM were amply documented. Diagnosis of severe renal failure secondary to MM was made. The patient chose multiple supports for RFR. The following naturopathic renal supplements were prescribed: Uristatin (2 capsules, BID), RenaPlex3 (2 capsules, BID), Kidney Stim Liquescence3 (1 dropper/day), Uriseptic Tea (3-4 c/day), Protease Concentrate HP3 (280 mg, BID), Phytodiuretic Formula3 (1 dropper BID) and MultiB Complex3 (1000 mg, BID). (8, 9) Nutritional counseling and constitutional hydrotherapy (hydrotherapy) (3/week) were also prescribed. Hydrotherapy, which employs application of alternating hot and cold towels to the patient’s abdomen and back, increases renal filtration and function by increasing the circulation of the arterial, venous and lymphatic systems (10). Follow-up appointments occurred every 2-3 weeks as the patient’s schedule allowed.

CCr measured 40.5 ml/min on August 20th. Dialysis was discontinued after 6 weeks, on August 24th, with SCr, 2.0 mg/dl. (Figure 1.) Despite a 3rd regimen of chemotherapy2 begun on August 12th, UPE M-proteins measured 4.5 g/day on August 27th. (Figure 1 on following page.)
Buoyed by a 1.8 mg/dl SCr on August 29th, the patient discontinued renal supplements and hydrotherapy without consulting the naturopathic physician. Only 6 hydrotherapy treatments had actually been received. SCr spikes continued occurring with uncontrolled MM. On September 16th, day 1 of the 4th regimen of chemotherapy2, SCr spiked to 3.9 mg/dl. Renal supplements and hydrotherapy (3/week) were reinstituted. SCr reduced to 2.1 mg/dl by September 21st. (Figure 1) Hydrotherapy was further increased to 4/week October 23rd in response to climbing UPE M-proteins (6.2 g/day, October 18th) and SCr spike (4.5 mg/dl) on October 22nd, the day the 5th regimen of chemotherapy chemotherapy was received. SCr then reduced to 2.7 mg/dl (October 28th) and 2.4 mg/dl (November 4th).(Figure 1.) On November 15th, UPE M-proteins measured 10.4 g/day – 242% of the level at which complete renal shutdown had occurred. (Figure 1.) Nevertheless, sufficient renal function had been maintained (SCr, 2.8 mg/dl and CCr, 32.3 ml/min on November 18th) for acceptance into a clinical trial of Velcade®. Due to rising SCr and UPE M-protein levels, on November 19th hydrotherapy was increased to 1/day at home, administered by caregiver. Despite November 20th bone marrow aspirate revealing >95% plasma cell neoplasm, SCr further reduced to 2.6 mg/dl on November 29th; BUN was 18 mg/dl. (Figure 1 on following page)

Velcade treatment began on December 2nd.Renal supplements were discontinued for the study. After the second Velcade dose, treatment was suspended by hospital- ization with febrile neutropenia December 6-10th. SCr rose to 5.6 mg/dl December 9th. Dialysis was recommended but declined (dialysis permanently barred participation in the Velcade study, the patient’s only hope for controlling his refractory MM). Further, no Velcade was possible with SCr >4.5 mg/dl. JSJ and home hydrotherapy treatments were combined and increased to 3/day December 9th, 2002 – January 16, 2003. Sufficient renal function was attained and maintained to receive Velcade on December 23rd. (Figure 1.) Near complete remission was confirmed January 16th and the patient has sought no further complementary care. No further dialysis has been required. On March 11, 2004, SCr was normal, 1.3 mg/dl.

Discussion

RFR in ESRD patients on dialysis has been reported at 1 – 2.4% and, in MM patients, at 6% (11, 12). It has not been possible to determine from the literature whether RFR of comparable magnitude and duration has ever been achieved in a similar case of complete renal failure and progressive, uncontrolled MM. While causation of RFR cannot be unambiguously asserted in this case, correlations are evident and consistent. Following both cessations of one or more of the regimen components, significant SCr spikes occurred. Further, all four major SCr spikes rapidly reduced with restored or increased complementary treatments, despite the mounting renal pressures of uncontrolled MM (Figure 1). Notably, with increased daily home hydrotherapy, SCr and BUN actually improved slightly two weeks after the apex UPE M-protein measurement of November 15th. (Figure 1) Such correlations appear to indicate the whole practice restored sufficient renal function to allow for participation in the Velcade study, both initially and on December 23rd, thereby extending the patient’s survival.
The interventions we are reporting offer forms of support for RFR that are otherwise unavailable. We theorize that: 1) the increased pumping action afforded by hydrotherapy may function to expel M-proteins lodged in the myeloma kidney, minimizing long term renal damage; 2) JSJ provides additional energy for maintaining vitality and allowing for healing of damaged renal tissue; and 3) the supplements provide more targeted support for renal issues.

Disadvantages of treatment

Though no problems have been reported, hydrotherapy may increase the rate at which chemotherapeutics are metabolized, so caution should be exercised in treatment timing. The supplements increased an already large volume of oral medications being taken by the patient and were associated with increased nausea. Too, the pharmacist regarded some of the herbal ingredients as potentially nephrotoxic. Without other options and with consistent evidence of rapidly decreasing SCr, the patient chose to continue the supplements. All of the interventions share a primary disadvantage of complementary therapies, cost. Costs are substantial and are not typically covered by insurance. Additional time burdens are also involved.

Conclusions

The whole practice regimen is likely to have played a key role in allowing RFR to occur. Each patient is unique, however. Additional reports on other patients receiving the regimen are necessary to determine a general benefit. Any future clinical trials should identify any specific role(s) played by treatment component(s) and/or whether a synergistic effect is allowed by the whole practice.

Figure 1

Legend, Figure 1:

Figure 1: Creatinine measured in serum of the subject and urinary M-protein levels measured by electrophoresis (UPE) are shown over time. Serum creatinine is on the left-hand y-axis, while urinary M-proteins are on the right- hand y-axis. Cessation of treatment component(s) on 8/29/02 and 12/2/02 are shown with down arrows. Restoration or increases in treatment components (9/16/02; 10/22/02; 11/19/02; 12/09/02) are shown with up arrows.

References

1. Clark AD, Shetty A, Soutar R. Renal failure and multiple myeloma: pathogenesis and treatment of renal failure and management of underlying myeloma. Blood Rev 1999 Jun; 13(2):79-90.
2. Cengic M, Robovic Z, Rasic S, Golemac S. [Relation between certain parameters of renal function and prognosis in multiple myeloma.] Med Arh 2001;55(4):193-5. Croatian. Abstract only.
3. Alexanian R, Barlogie B, Dixon D. Renal failure in multiple myeloma. Pathogensis and prognostic implications. Arch Intern Med 1990;150(8):1693-5.
4. Sakhuja V, Jha V, Varma S, Joshi K, Gupta KL, Sud K, et al. Renal involvement in multiple myeloma: a 10-year study. Ren Fail 2002;22(4):465-77.
5. Knudsen LM, Hjorth M, Hippe E. Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol 2000 Sep;65(3):175-81.
6. Shannon AR. Jin Shin Jyutsu treatment outcomes in a patient with multiple myeloma. Altern Ther Health Med 2002 Sep-Oct;8(5):128,126-7.
7. Burmeister, Mary. Text II: Jin Shin Jyutsu® Physio Philosophy. Scottsdale, AZ: Jin Shin Jyutsu®, Inc. 1997; pp. 17,27.
8. Boik J. Natural compounds in cancer therapy. Princeton, MN: Oregon Medical Press. 2002.
9. Boik J. Cancer and natural medicine: a textbook of basic science and clinical research. Princeton, MN: Oregon Medical Press. 1996.
10. Boyle W, Saine A. Lectures in Naturopathic Hydrotherapy. East Palestine, OH: Buckeye Naturopathic Press. 1988.
11. Agraharkar M, Nair V, Patlovany M. Recovery of renal function in dialysis patients. BMC Nephrol 2003 Oct 16;4(1)9.
12. Pichette V, Querin S, Desmeules M, Ethier J, Copleston P. Renal function recovery in end-stage renal disease. Am J Kidney Dis 1993 Sep;22(3):398- 402.
International Journal of Naturopathic Medicine 2004; 1(1): 21

Commentary

This case highlights how Naturopathic interventions may be integrated with and complement orthodox medical therapies. While case studies do not provide definitive evidence of efficacy and do not lend to the establishment of cause and effect arguments, it is hard to overlook the improvements in this patient’s condition coinciding with the Naturopathic interventions employed. Individuals with ESRD resulting from MM rarely achieve normal renal function. As the authors indicate, it is possible that the Naturopathic interventions employed allowed this patient to regain significant renal function so as to be eligible for inclusion in to the Velcade trial, which ultimately allowed the patient go into remission. Bortezomid (Velcade), a proteasome inhibitor, is a new drug that shows great promise in the treatment of MM. Phase I and II clinical trials are beginning to delineate its’ efficacy, especially in refractory cases.

The use of Naturopathic interventions to allow patients to undergo specific procedures or enter into trials of new medications is an, as of yet, unexplored area of “complemen- tary” health-care. Again, while it is not clear that the Naturopathic interventions employed in this case caused the improvement in renal functional measures, temporality suggests it. Future clinical trials could test this hypothesis and other questions that ask about how complementary and alternative medicines can be used as preparatory treatments for other interventions.

Joel J. Gagnier B.A.(Hons), N.D., M.Sc.(Cand. Clin. Epi.) Deputy Editor, International Journal of Naturopathic Medicine Associate Professor, Associate Director of Research, Canadian College Of Naturopathic Medicine CIHR-ONHP Fellow in the Faculty of Medicine, University of Toronto