Kidney International, Vol. 60 (2001), pp. 1201–1202

LETTER TO THE EDITOR

concentration when nephrologists face uremic depres-Depression in dialysission? If rubidium deficiency is confirmed, it might allowsupplementation, which could add to the tools for thepatients: Rubidiumwar against uremic depression.

supplementation before other Caterina Canavese, Ester DeCostanzi,Lino Branciforte, Antonio Caropreso,

Antonello Nonnato, and Enrico Sabbionidrugs and encouragement?Torino and Varese, Italy

Correspondence to Caterina Canavese, M.D., Department of InternalTo the Editor: We read with interest the NephrologyMedicine, Section of Nephrology, S. Giovani Molinette Hospitale, Corso

Forum of Professor Kimmel regarding psychosocial fac- Bramante 88, 1026 Torino, Italy.E-mail: ccanavese@hotmail.comtors in dialysis patients, in which depression is carefully

reviewed [1]. Rather surprising, the participants discussREFERENCES“abnormal cytokine regulation” in the pathogenesis of

uremic depression, but no mention is made of the possi- 1. Kimmel PL: Psychosocial factors in dialysis patients. Kidney Intble role of trace elements abnormalities, such as rubid- 59:1599–1613, 2001

2. Krachler M, Wirnsberger GH: Long-term changes of plasma traceium. However, it is well-known that rubidium acts atelement concentrations in chronic hemodialysis patients. Bloodthe level of the central nervous system (CNS) [2] by Purif 18(2):138–143, 2000

increasing synaptic neurotransmitter levels, thus allow- 3. Meltzer HL, Taylor RM, Platman SR, Fieve RR: Rubidium: Apotential modifier of effect and behaviour. Nature 223:321–322, 1969ing the introduction of rubidium-based compounds as

4. Canavese C, DeCostanzi E, Branciforte L, et al: Rubidium deficiencyantidepressant drugs, with an efficacy as high as that of in dialysis patients. J Nephrol 14(3): 169–175, 2001tricyclic agents, and with fewer side effects. Furthermore,many data prove that a true rubidium deficiency occursin dialysis patients [3, 4]: (1) reduced tissue, including

Reply from the authorCNS (2250 � 1520 ng/g vs. 5490 � 1250 ng/g, P � 0.0002)Canavese et al raise the interesting notion that abnor-rubidium concentrations (Fig. 1); (2) lower serum rubid-

malities in trace elemental metabolism may be linkedium concentrations compared with normal people (304 �with depression in patients treated for end-stage renal81 �g/L vs. 350 � 74 �g/L, P � 0.001) with odd ratiosdisease (ESRD) with hemodialysis (HD). This raisesfor rubidum �250 �g/L � 12.6, 95% CI 2.77 to 57.04;points regarding the pluralistic aspects of assessing de-(3) low rubidium content (�2 �g/L) in solutions em-pressive effect in patients with chronic medical illnessesployed for hemodialysis and intraperitoneal dialysis; and[1, 2]. Rubidium plays a role in neurotransmission and(4) negative intradialytic rubidium balance (4.0 � 1.1transport processes [3], as does zinc in mediating enzymemg/session).activity and gene expression [3, 4]. Indeed, abnormalObviously, rubidium supplementation cannot modifyzinc metabolism has been linked to both inflammationthe burden of the illness, just as all the other therapeutic

options did not [1]. However, why not look for rubidium and depression in patients in both the absence of renal

Fig. 1. Rubidium concentrations in tissues ofdialysis patients (�) compared with normalpeople ( ).

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Letter to the Editor1202

disease [5–8] and in its presence [4]. Abnormalities in changes in meaningful and well-measured psychosocialoutcomes. Hopefully, over the next decade, we will makemineral metabolism in hemodialysis patients may impact

multiple physiologic processes that can be associated strides in identifying and understanding any relationshipsthat may exist between the disordered physiology ofwith decreased feelings of well-being or with neurologic

dysfunction. There are few data on the relationship be- chronic renal disease and mental disorders in our patients.tween cellular cytokine production and circulating cyto-

Paul L. Kimmelkines and mineral metabolism in the ESRD populationBethesda, MD, USA[9, 10], and even fewer linking cytokine metabolism to

psychosocial factors. Space limitations, however, did not Correspondence to Paul L. Kimmel, M.D., Division of Kidney, Uro-logic and Hematologic Diseases, National Institutes of Diabetes, Diges-permit full consideration of this little-studied field in thetive and Kidney Diseases, National Institutes of Health, Bethesda, MD,

Nephrology Forum. Of note, however, an early small and Division of Renal Diseases and Hypertension, Department of Medi-cine, George Washington University Medical Center, Washington, D.C.study of the effect of zinc supplementation in HD pa-E-mail: kimmelp@extra.niddk.nih.govtients did not produce a change in measures of depres-

sion [11].REFERENCESHowever, it is important to maintain the perspective

1. Kimmel PL: Psychosocial factors in dialysis patients. Nephrologythat the pathophysiology of the mental illness, depres-Forum. Kidney Int 59:1599–1613, 2001sion, is not fully understood, and that nephrologists must

2. Kimmel PL, Weihs KL, Peterson RA: Depression and survivaldistinguish the symptoms of depression (which are com- in hemodialysis patients. J Am Soc Nephrol 4:12–27, 1994

3. Zima T, Tesar V, Mesteck O, Nemecek K: Trace elements in end-mon in uremia) from the clinical syndrome bearing thestage renal disease. 2. Clinical implication of trace elements. Bloodsame name, and from encephalopathy and other neuro-Purif 17:187–198, 1999

logic disorders. For nephrologists, in this regard, two 4. Kimmel PL: Zinc and chronic renal disease. Semin Dialysis 2:253–259, 1989notions are of quintessential importance: (1) optimizing

5. Maes M, Bosmans E, De Jongh R, et al: Increased serum IL-6the medical care of the patient, which includes the metic- and IL-1 receptor antagonist concentrations in major depressionulous attention to the multiple organ system derange- and treatment resistant depression. Cytokine 9:853–858, 1997

6. Maes M, Vandoolaeghe E, Neels H, et al: Lower serum zinc inments that typify uremia, and may confound our diagno-major depression is a sensitive marker of treatment resistancesis of depression [1, 2], and (2) the making of causal and of the immune/inflammatory response in that illness. Biol

assumptions that are not supported by rigorous and well- Psychiatry 42:349–358, 19977. Nowak G: Alterations in zinc homeostasis in depression and anti-designed studies.

depressant therapy. Pol J Pharmacol 50:1–4, 1998The field of mental disorders in patients with chronic 8. Maes M, De Vos N, Demedts P, et al: Lower serum zinc in majorrenal disease is wide open and amenable to the design depression in relation to changes in serum acute phase proteins.

J Affect Disord 56:189–194, 1999and implementation of interventions, including those in-9. Kimmel PL, Phillips TM, Lew SQ, Langman CB: Zinc modulatesvolving optimizing patient care and treating trace min- mononuclear cell calcitriol metabolism in peritoneal dialysis pa-

eral metabolic abnormalities, while observing subsequent tients. Kidney Int 49:1407–1412, 199610. Kimmel PL, Phillips TM, Simmens SJ, et al: Immunologic function

and survival in hemodialysis patients. Kidney Int 54:236–244, 199811. Zetin M, Stone RA: Effects of zinc in chronic hemodialysis. Clin

2001 by the International Society of Nephrology Nephrol 13:20–25, 1980